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Background: HTLV-1 is a worldwide distribution retrovirus with 10–20 million infected individuals. ATLL is an Adult T-cell leukaemia lymphoma caused by aggressive T-cell proliferation that is infected by HTLV-1 and is associated with an inferior prognosis. The exact molecular pathogenesis has yet to be fully understood. CREB, a transcription factor, acts as a molecular switch that controls the expression of numerous genes in response to various extracellular signals. Its activation is primarily mediated through phosphorylation by multiple kinases, including MAPKs. MAPKs, a family of serine/threonine kinases, serve as crucial mediators of intracellular signaling cascades. Method and material: This study investigated, 38 HTLV-I-infected individuals, including 18 HTLV-1 asymptomatic carriers (ACs) and 20 ATLL subjects. mRNA was extracted and converted to cDNA from Peripheral blood mononuclear cells (PBMCs), and then the expression of TAX, HBZ, CREB, and MAPK was analyzed by TaqMan qPCR. The genomic HTLV-1 Proviral loads were examined among the study group. Results: The data analysis showed a significant difference in the mean of CREB expression amongst study groups (ATLL and carriers, (p = 0.002). There is no statistical difference between the MAPK gene expression (p = 0.35). HBZ, TAX, and HTLV-1 proviral load weree significantly higher in ATLL subjects compared to ACs (p = 0.002, 0.000, and 0.000), respectively. Moreover, our results, demonstrated a direct positive correlation among HBZ, CREB, and TAX gene expression in ATLL patients (p = 0.001), whilst between the ACs, TAX gene expression had a positive significant correlation with HBZ and HTLV-1 proviral load (p = 0.007 and p = 0.004, respectively). Conclusion: The present study demonstrated that CREB gene expression was higher in the ATLL group than ACs, while there was no difference for MAPK. Therefore, this pathway may not strongly involve in the activation of CREB. The CREB may be a prognostic factor for the development of HTLV-I-associated diseases and can be used as a monitoring marker for the efficiency of the therapeutic regime and prognosis. [ABSTRACT FROM AUTHOR]

Background: Avian leukosis virus subgroup J (ALV‐J) primarily affects poultry, particularly chickens, leading to tumourigenesis and immunosuppression, which results in substantial economic losses. It is important to note that ALV‐J is commonly found in indigenous chicken breeds in China, and the virus's vertical transmission characteristics present a significant threat to the preservation of local chicken breeds. Objectives: The study aimed to investigate the characteristics and effects of the recombinant ALV‐J strain LY2021J, with a focus on its genetic composition and its potential influence on virulence and pathogenicity. Methods: LY2021J was isolated using DF‐1 cells and validated by enzyme‐linked immunosorbent assay (ELISA) and IFA. The proviral genome was amplified using segmented PCR and then spliced together using DNASTAR software. Genome‐wide genes, including gag, pol, gp85, and long terminal repeat (LTR), were compared. Recombination sites were analysed using RDP5 and SimPlot software. Pathogenicity was evaluated by monitoring symptoms and conducting examinations on SPF chickens. Results: The outbreak of ALV‐J in China has caused significant economic losses in the poultry industry. Although largely controlled in white‐feather broilers and egg‐laying chickens, ALV‐J has spread to yellow‐feather broilers and local breeds. A strain, LY2021J, isolated from Hetian chickens, showed lower mortality despite severe dysplasia. Genetic analysis revealed high similarity between LY2021J and the Chinese strains JS14NT01 and NX0101, suggesting a shared origin. Recombination with strain ev‐1 and specific 3′ UTR deletions may explain LY2021J's reduced virulence. Continued monitoring and prevention strategies are essential to mitigate ALV‐J's impact. [ABSTRACT FROM AUTHOR]

The Conference on Retroviruses and Opportunistic Infections (CROI) is usually the most significant HIV conference of the year in terms of basic and clinical scientific output. CROI 2024 in Denver, USA, felt very much back to 'business as usual' following COVID‐19 disruptions that had impacted preceding years, but also felt more global and outward‐ facing. The British HIV Association supports a working group to attend CROI annually and deliver feedback in the UK. This article summarizes the highlights from that meeting. [ABSTRACT FROM AUTHOR]

Proteasomes are barrel-like cellular protein complexes responsible for the degradation of most intracellular proteins. Earlier, it has been shown that during assembly, hundreds of different cellular proteins are incorporated into retro-and herpes viruses. Among detected cellular proteins, there were different proteasome subunits (PS). Previous reports postulated the incorporation of 20S proteasome subunits and subunits of proteasome regulator complexes inside retroviruses. Here, we demonstrated the association of functional 20S proteasome with gammaretroviruses, betaretroviruses, and lentiviruses. Cleaved proteasome subunits β1, β2 and β5 were detected in tested viruses. Using fluorescent peptides and a cell-permeable proteasome activity probe, proteasome activity was detected in endogenous and exogenous retroviruses, including recombinant HIV-1. Taken together, our data favors the insertion of functional proteasomes into the retroviruses during assembly. The possible role of proteasomes in retroviruses is discussed. [ABSTRACT FROM AUTHOR]

Porcine endogenous retroviruses (PERVs) are integrated in the genome of all pigs. PERVA, PERV-B and PERV-C can be released as infectious virus particles and PERV-A and PERV-B can infect human cells in culture. PERV-C does not infect human cells, but hightiter recombinant PERV-A/C can infect them. Retroviruses are able to induce immunosuppression and/or tumors in the infected host. Numerous methods have been developed to study PERV in donor pigs. No PERV infections were observed in infection experiments as well as in preclinical and clinical xenotransplantation trials. Despite this, several strategies have been developed to prevent PERV infection of the recipient. PCR-based and immunological methods are required to screen xenotransplant recipients. Since the proviruses are integrated into the pig genome, PERV infection has to be distinguished from microchimerism, e.g., the presence of pig cells in the recipient, which is common in xenotransplantation. Sensitive PCR methods using pig short interspersed nuclear elements (SINE) sequences allow to detect pig cells easily. Virus infection can also be detected by an increase of viral genomic or mRNA in human cells. The method of choice, however, is to screen for specific antibodies against PERV using different recombinant PERV proteins, purified viruses or peptides. [ABSTRACT FROM AUTHOR]

The human genome harbors many endogenous retroviral elements, known as human endogenous retroviruses (HERVs), which have been integrated into the genome during evolution due to infections by exogenous retroviruses. Accounting for up to 8% of the human genome, HERVs are tightly regulated by the host and are implicated in various physiological and pathological processes. Aberrant expression of HERVs has been observed in numerous studies on exogenous viral infections. In this review, we focus on elucidating the potential roles of HERVs during various exogenous viral infections and further discuss their implications in antiviral immunity. [ABSTRACT FROM AUTHOR]

Retroviruses perpetuate their survival by incorporating a copy of their genome into the host cell, a critical step catalyzed by the virally encoded integrase. The viral capsid plays an important role during the viral life cycle, including nuclear importation in the case of lentiviruses and integration targeting events; hence, targeting the integrase and the viral capsid is a favorable therapeutic strategy. While integrase strand transfer inhibitors (INSTIs) are recommended as first-line regimens given their high efficacy and tolerability, lenacapavir is the first capsid inhibitor and the newest addition to the HIV treatment arsenal. These inhibitors are however designed for treatment of HIV-1 infection, and their efficacy against HIV-2 remains widely understudied and inconclusive, supported only by a few limited phenotypic susceptibility studies. We therefore carried out inhibition profiling of a panel of second-generation INSTIs and lenacapavir against HIV-2 in cell culture, utilizing pseudovirion inhibition profiling assays. Our results show that the tested INSTIs and lenacapavir exerted excellent efficacy against ROD-based HIV-2 integrase. We further evaluated the efficacy of raltegravir and other INSTIs against different variants of SARS-CoV-2; however, contrary to previous in silico findings, the inhibitors did not demonstrate significant antiviral activity. [ABSTRACT FROM AUTHOR]

Objective: This paper aims to review the risks associated with using lentiviral and retroviral vectors in research and clinical settings and to propose an update to an effective treatment plan. Methods: Risks of exposure were evaluated based on vector design, safety features, viral tropism, transgene, and means and modes of transmission. These risks wereweighed against the potential risks and benefits of current HIV medications. Results:We recommend the following postexposure prophylactic treatment for significant lentiviral vector exposures: 1) dolutegravir 50 mg taken once a day for 7 days and 2) tenofovir disoproxil fumarate 300 mg taken once a day for 7 days (28 days of both medications for replication-competent vectors). Conclusions: Because of the highly efficient delivery of transgenes by modern lentiviral and retroviral vectors, postexposure prophylaxis is indicated to prevent vector integration and oncogenic risks. [ABSTRACT FROM AUTHOR]

Introduction: Breast cancer is the most common cancer and the leading cause of cancer death in women. Recent research indicates that human endogenous retroviruses (HERVs) may be linked to carcinogenesis, but the data remain controversial. Methods: HERVs' expression was evaluated to show the differences between breast cancer and control samples, and their associations with clinicopathological parameters. Gene expression of 12 HERVs, i.e., ERVE-4, ERVW-1, ERVFRD-1, ERVV-1, ERV3-1, ERVH48-1, ERVMER34-1, ERVK-7, ERVK13-1, ERVK11-1, ERVK3-1, and HCP5, was analyzed by qPCR and/or TCGA datasets for breast cancer. Results: ERV3-1, ERVFRD-1, ERVH48-1, and ERVW-1 provided data to support their tumor suppressor roles in breast cancer. ERV3-1 evinced the best performing diagnostic data based on qPCR, i.e., AUC: 0.819 (p < 0.0001), sensitivity of 72.41%, and specificity of 89.66%. Lower levels of ERV3-1 were noted in advanced stage and higher grades, and significant negative association was found in relation to Ki-67 levels. Oncogenic roles may be inferred for ERVK13-1, ERVV-1, and ERVMER34-1. Data for ERVK-7, ERVE-4, ERVK11-1, and HCP5 remain inconclusive. Conclusion: Differential HERV expression may be applicable to evaluate novel biomarkers for breast cancer. However, more research is needed to reveal their real clinical impact, the biological roles, and regulatory mechanisms in breast carcinogenesis. [ABSTRACT FROM AUTHOR]

The HIV‐1 protease is critical for the process of viral maturation and as such, it is one of the most well characterized proteins in the Protein Data Bank. There is some evidence to suggest that the HIV‐1 protease is capable of accommodating small molecule fragments at several locations on its surface outside of the active site. However, some pockets on the surface of proteins remain unformed in the apo structure and are termed "cryptic sites." To date, no cryptic sites have been identified in the structure of HIV‐1 protease. Here, we characterize a novel cryptic cantilever pocket on the surface of the HIV‐1 protease through mixed‐solvent molecular dynamics simulations using several probes. Interestingly, we noted that several homologous retroviral proteases exhibit evolutionarily conserved dynamics in the cantilever region and possess a conserved pocket in the cantilever region. Immobilization of the cantilever region of the HIV‐1 protease via disulfide cross‐linking resulted in curling‐in of the flap tips and the propensity for the protease to adopt a semi‐open flap conformation. Structure‐based analysis and fragment‐based screening of the cryptic cantilever pocket suggested that the pocket may be capable of accommodating ligand structures. Furthermore, molecular dynamics simulations of a top scoring fragment bound to the cryptic pocket illustrated altered flap dynamics of the fragment‐bound enzyme. Together, these results suggest that the mobility of the cantilever region plays a key role in the global dynamics of retroviral proteases. Therefore, the cryptic cantilever pocket of the HIV‐1 protease may represent an interesting target for future in vitro studies. [ABSTRACT FROM AUTHOR]

Transposable elements (TEs) comprise a substantial portion of the mammalian genome, with potential implications for both embryonic development and cancer. This study aimed to characterize the expression profiles of TEs in embryonic stem cells (ESCs), cancer cell lines, tumor tissues, and the tumor microenvironment (TME). We observed similarities in TE expression profiles between cancer cells and ESCs, suggesting potential parallels in regulatory mechanisms. Notably, four TE RNAs (HERVH, LTR7, HERV-Fc1, HERV-Fc2) exhibited significant downregulation across cancer cell lines and tumor tissues compared to ESCs, highlighting potential roles in pluripotency regulation. The strong up-regulation of the latter two TEs (HERV-Fc1, HERV-Fc2) in ESCs has not been previously demonstrated and may be a first indication of their role in the regulation of pluripotency. Conversely, tandemly repeated sequences (MSR1, CER, ALR) showed up-regulation in cancer contexts. Moreover, a difference in TE expression was observed between the TME and the tumor bulk transcriptome, with distinct dysregulated TE profiles. Some TME-specific TEs were absent in normal tissues, predominantly belonging to LTR and L1 retrotransposon families. These findings not only shed light on the regulatory roles of TEs in both embryonic development and cancer but also suggest novel targets for anti-cancer therapy. Understanding the interplay between cancer cells and the TME at the TE level may pave the way for further research into therapeutic interventions.

Abstract Retroviruses exploit host proteins to assemble and release virions from infected cells. Previously, most studies focused on interacting partners of retroviral Gag proteins that localize to the cytoplasm or plasma membrane. Given that several full-length Gag proteins have been found in the nucleus, identifying the Gag-nuclear interactome has high potential for novel findings involving previously unknown host processes. Here we systematically compared nuclear factors identified in published HIV-1 proteomic studies and performed our own mass spectrometry analysis using affinity-tagged HIV-1 and RSV Gag proteins mixed with nuclear extracts. We identified 57 nuclear proteins in common between HIV-1 and RSV Gag, and a set of nuclear proteins present in our analysis and ≥ 1 of the published HIV-1 datasets. Many proteins were associated with nuclear processes which could have functional consequences for viral replication, including transcription initiation/elongation/termination, RNA processing, splicing, and chromatin remodeling. Examples include facilitating chromatin remodeling to expose the integrated provirus, promoting expression of viral genes, repressing the transcription of antagonistic cellular genes, preventing splicing of viral RNA, altering splicing of cellular RNAs, or influencing viral or host RNA folding or RNA nuclear export. Many proteins in our pulldowns common to RSV and HIV-1 Gag are critical for transcription, including PolR2B, the second largest subunit of RNA polymerase II (RNAPII), and LEO1, a PAF1C complex member that regulates transcriptional elongation, supporting the possibility that Gag influences the host transcription profile to aid the virus. Through the interaction of RSV and HIV-1 Gag with splicing-related proteins CBLL1, HNRNPH3, TRA2B, PTBP1 and U2AF1, we speculate that Gag could enhance unspliced viral RNA production for translation and packaging. To validate one putative hit, we demonstrated an interaction of RSV Gag with Mediator complex member Med26, required for RNA polymerase II-mediated transcription. Although 57 host proteins interacted with both Gag proteins, unique host proteins belonging to each interactome dataset were identified. These results provide a strong premise for future functional studies to investigate roles for these nuclear host factors that may have shared functions in the biology of both retroviruses, as well as functions specific to RSV and HIV-1, given their distinctive hosts and molecular pathology. Graphical Abstract

During the past two decades evidence has been developed that indicates a handful of viruses with known oncogenic capacity, have potential roles in breast cancer. These viruses are mouse mammary tumour virus (MMTV - the cause of breast cancer in mice), high-risk human papilloma viruses (HPV-the cause of cervical cancer), Epstein Barr virus (EBV-the cause of lymphomas and naso-pharyngeal cancer) and bovine leukemia virus (BLV - the cause of cancers in cattle). These viruses may act alone or in combination. Each of these viruses are significantly more prevalent in breast cancers than in normal and benign breast tissue controls. The odds ratios for the prevalence of these viruses in breast cancer compared to normal and benign breast controls, are based on case control studies - MMTV 13·40, HPV 5.56, EBV 4·43 and BLV 2·57. The odds ratios for MMTV are much greater compared to the other three viruses. The evidence for a causal role for mouse mammary tumour virus and high risk for cancer human papilloma viruses in human breast cancer is increasingly comprehensive. The evidence for Epstein Barr virus and bovine leukemia virus is more limited. Overall the evidence is substantial in support of a viral cause of breast cancer. [ABSTRACT FROM AUTHOR]

Retroviruses are an ancient viral family that have globally coevolved with vertebrates and impacted their evolution. In Australia, a continent that has been geographically isolated for millions of years, little is known about retroviruses in wildlife, despite the devastating impacts of a retrovirus on endangered koala populations. We therefore sought to identify and characterize Australian retroviruses through reconstruction of endogenous retroviruses from marsupial genomes, in particular the Tasmanian devil due to its high cancer incidence. We screened 19 marsupial genomes and identified over 80,000 endogenous retrovirus fragments which we classified into eight retrovirus clades. The retroviruses were similar to either Betaretrovirus (5/8) or Gammaretrovirus (3/8) retroviruses, but formed distinct phylogenetic clades compared to extant retroviruses. One of the clades (MEBrv 3) lost an envelope but retained retrotranspositional activity, subsequently amplifying throughout all Dasyuridae genomes. Overall, we provide insights into Australian retrovirus evolution and identify a highly active endogenous retrovirus within Dasyuridae genomes. [ABSTRACT FROM AUTHOR]

Introduction: The dysbiosis of vaginal microbiota is recognized as a potential underlying factor contributing to infertility in women. This study aimed to compare the vaginal microbiomes of infertile and fertile women to investigate their relationship with infertility. Methods: Metagenomic analysis was conducted on samples from 5 infertile and 5 fertile individuals using both amplicon 16S and metagenomics shotgun sequencing methods. Results and discussion: In the infertile group, the bacterial community was primarily represented by three major bacterial genera: Lactobacillus (79.42%), Gardnerella (12.56%) and Prevotella (3.33%), whereas, the fertile group exhibited a more diverse composition with over 8 major bacterial genera, accompanied by significantly reduced abundance of Lactobacillus (48.79%) and Gardnerella (6.98%). At the species level, higher abundances of L. iners, L. gasseri and G. vaginalis were observed in the infertile group. Regarding the microbiome composition, only one fertile and two infertile subjects exhibited the healthiest Community State Types, CST-1, while CST-3 was observed among two infertile and one fertile subject, and CST-4 in three other fertile and one infertile subject. Overall, alpha diversity metrics indicated greater diversity and lower species richness in the control (fertile) group, while the infertile group displayed the opposite trend. However, beta-diversity analysis did not show distinct clustering of samples associated with any specific group; instead, it demonstrated CST-type specific clustering. Shotgun metagenomics further confirmed the dominance of Firmicutes, with a greater abundance of Lactobacillus species in the infertile group. Specifically, L. iners and G. vaginalis were identified as the most dominant and highly abundant in the infertile group. Fungi were only identified in the control group, dominated by Penicillium citrinum (62.5%). Metagenomeassembled genomes (MAGs) corroborated read-based taxonomic profiling, with the taxon L. johnsonii identified exclusively in disease samples. MAG identities shared by both groups include Shamonda orthobunyavirus, L. crispatus, Human endogenous retrovirus K113, L. iners, and G. vaginalis. Interestingly, the healthy microbiomes sequenced in this study contained two clusters, Penicillium and Staphylococcus haemolyticus, not found in the public dataset. In conclusion, this study suggests that lower species diversity with a higher abundance of L. iners, L. gasseri and G. vaginalis, may contribute to female infertility in our study datasets. However, larger sample sizes are necessary to further evaluate such association. [ABSTRACT FROM AUTHOR]

Several viruses have been implicated in breast cancer, including human herpes virus 4 (HHV4), human herpes virus 5 (HHV5), human papilloma virus (HPV), human JC polyoma virus (JCV), human endogenous retrovirus group K (HERVK), bovine leukemia virus (BLV) and mouse mammary tumor virus (MMTV). Human leukocyte antigen (HLA) is involved in virus elimination and has been shown to influence breast cancer protection/susceptibility. Here we investigated the hypothesis that the contribution of a virus to development of breast cancer would depend on the presence of the virus, which, in turn, would be inversely related to the success of its elimination. For that purpose, we estimated in silico predicted binding affinities (PBA) of proteins of the 7 viruses above to 127 common HLA alleles (69 Class I [HLA-I] and 58 Class II HLA-II]) and investigated the association of these binding affinities to the breast cancer—HLA (BC-HLA) immunogenetic profile of the same alleles. Using hierarchical tree clustering, we found that, for HLA-I, viruses BLV, JCV and MMTV were grouped with the BC-HLA, whereas, for HLA-II, viruses BLV, HERVK, HPV, JCV, and MMTV were grouped with BC-HLA. Finally, for both HLA classes, the average PBAs of the viruses grouped with the BC-HLA profile were significantly lower than those of the other, non BC-HLA associated viruses. Assuming that low PBAs are likely associated with slower viral elimination, these findings support the hypothesis that a defective/slower elimination and, hence, longer persistence and inefficient/delayed production of antibodies against them underlies the observed association of the low-PBA group with breast cancer. [ABSTRACT FROM AUTHOR]

Peptide nanofibrils (PNFs) are considered a novel and highly efficient class of retroviral transduction enhancers due to their ability to efficiently bind virus particles and promote their attachment to the membrane of target cells. In this study, the virus‐binding properties of enhancing factor C (EF‐C) PNFs are used to develop a method for concentrating and isolating HIV‐1 particles without the need for centrifugation. Upon incubation in a virus‐laden sample, PNF‐coated magnetic beads facilitate magnetic separation, effectively depleting virus particles from the solution and consequently reducing its infectious nature. Remarkably, the isolated virus particles maintain their infectivity and exhibit an enhanced ability to infect target cells due to the complexation with EF‐C PNFs. This enhancement is pivotal for further virus propagation in cell cultures or detailed analysis. The presented method addresses the urgent need for more rapid, sensitive detection, and purification technologies for viral agents. It provides a tool to efficiently capture, isolate, and concentrate HIV‐1 particles. This may significantly improve the sensitivity of existing diagnostic tools and analytical tests. [ABSTRACT FROM AUTHOR]

The evolutionary pressures exerted by viral infections have led to the development of various cellular proteins with potent antiviral activities, some of which are known as antiviral restriction factors. TRIpartite Motif-containing protein 5 alpha (TRIM5α) is a well-studied restriction factor of retroviruses that exhibits virus- and host-species-specific functions in protecting against cross-primate transmission of specific lentiviruses. This specificity is achieved at the level of the host gene through positive selection predominantly within its C-terminal B30.2/PRYSPRY domain, which is responsible for the highly specific recognition of retroviral capsids. However, more recent work has challenged this paradigm, demonstrating TRIM5α as a restriction factor for retroelements as well as phylogenetically distinct viral families, acting similarly through the recognition of viral gene products via B30.2/PRYSPRY. This spectrum of antiviral activity raises questions regarding the genetic and structural plasticity of this protein as a mediator of the recognition of a potentially diverse array of viral molecular patterns. This review highlights the dynamic evolutionary footprint of the B30.2/PRYSPRY domain in response to retroviruses while exploring the guided 'specificity' conferred by the totality of TRIM5α's additional domains that may account for its recently identified promiscuity. [ABSTRACT FROM AUTHOR]

Introduction: The Vel– phenotype is a rare blood group, and it is challenging for identifying this phenotype due to limited available reagents. Moreover, there are relatively few studies on genomic editing of erythroid antigens and generation of knockout (KO) cell lines at present. Methods: To identify the high-efficiency small-guiding RNA (sgRNA) sequence, candidate sgRNAs were transfected into HEK 293T cells and analyzed using Sanger sequencing. Following this, the high-efficiency sgRNA was transfected into K562 cells using lentivirus transduction to generate KO Vel blood group gene cells. The expression of the Vel protein was detected using Western blot on single-cell clones. Additionally, flow cytometry was used to detect the erythroid markers CD235a and CD71. Hemoglobin quantification and Giemsa staining were also performed to evaluate the erythroid differentiation of KO clones induced by hemin. Results: The high-efficiency sgRNA was successfully obtained and used for CRISPR-Cas9 editing in K562 cells. After limiting dilution and screening, two KO clones had either deleted 2 or 4 bases and showed no expression of the Vel protein. In the hemin-induced KO clone, there was a significant difference in erythroid marker and hemoglobin quantification compared to untreated cells. The morphological changes were also observed for the hemin-induced KO clone. Conclusion: In this study, a highly efficient sgRNA was screened out and used to generate Vel erythroid antigen KO single-cell clones in K562 cells. The edited cells could then be induced to undergo erythroid differentiation with the use of hemin. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to identify knowledge gaps in the global prevalence of feline immunodeficiency virus (FIV) and to obtain professional opinions and experiences regarding FIV in selected countries. We conducted a literature review of abstracts that reported the prevalence of FIV and interviewed experts in feline medicine and retroviruses from different countries to determine regional perspectives. Methods: A total of 90 articles reporting FIV prevalence as a primary unbiased population-level analysis between 1980 and 2017 were indexed. FIV prevalence, demographics, year and location were analyzed. Statistics were evaluated and compared. In total, 10 experts were interviewed. Results were analyzed for congruence with the findings of the literature review. Results: FIV prevalence was typically in the range of 5–8%, with a global prevalence of 4.7%, and remained largely constant over the reporting period (1980–2017). Over 90% of articles reported greater prevalence in older male cats. More studies were conducted in North America and Europe and reported the lowest prevalence. Expert-estimated prevalence approximated literature review prevalence. Attitudes and recommendations for management were consistent among experts. The limitations of the present review include varying inclusion criteria of cats tested in different studies, variation in testing modalities and the inability to conduct summary statistics across dissimilar cohorts. Conclusions and relevance: The global prevalence of FIV has not changed since its discovery 40 years ago. Prevalence is higher in older male cats and is lower in North America and Europe than other continents. Experts agree that FIV is not typically a disease of high concern and is often associated with infections of the oral cavity. Vaccination is not typically recommended and has been discontinued in North America. The evaluation of risk factors for FIV progression is useful in managing infections. Recommendations for future research include analyses to determine copathogen and environmental factors that impact progression, assessment of life span impacts and investigations of treatment efficacy and side effects. [ABSTRACT FROM AUTHOR]

Retroviruses exploit host proteins to assemble and release virions from infected cells. Previously, most studies focused on interacting partners of retroviral Gag proteins that localize to the cytoplasm or plasma membrane. Given that several full-length Gag proteins have been found in the nucleus, identifying the Gag-nuclear interactome has high potential for novel findings involving previously unknown host processes. Here we systematically compared nuclear factors identified in published HIV-1 proteomic studies and performed our own mass spectrometry analysis using affinity-tagged HIV-1 and RSV Gag proteins mixed with nuclear extracts. We identified 57 nuclear proteins in common between HIV-1 and RSV Gag, and a set of nuclear proteins present in our analysis and ≥ 1 of the published HIV-1 datasets. Many proteins were associated with nuclear processes which could have functional consequences for viral replication, including transcription initiation/elongation/termination, RNA processing, splicing, and chromatin remodeling. Examples include facilitating chromatin remodeling to expose the integrated provirus, promoting expression of viral genes, repressing the transcription of antagonistic cellular genes, preventing splicing of viral RNA, altering splicing of cellular RNAs, or influencing viral or host RNA folding or RNA nuclear export. Many proteins in our pulldowns common to RSV and HIV-1 Gag are critical for transcription, including PolR2B, the second largest subunit of RNA polymerase II (RNAPII), and LEO1, a PAF1C complex member that regulates transcriptional elongation, supporting the possibility that Gag influences the host transcription profile to aid the virus. Through the interaction of RSV and HIV-1 Gag with splicing-related proteins CBLL1, HNRNPH3, TRA2B, PTBP1 and U2AF1, we speculate that Gag could enhance unspliced viral RNA production for translation and packaging. To validate one putative hit, we demonstrated an interaction of RSV Gag with Mediator complex member Med26, required for RNA polymerase II-mediated transcription. Although 57 host proteins interacted with both Gag proteins, unique host proteins belonging to each interactome dataset were identified. These results provide a strong premise for future functional studies to investigate roles for these nuclear host factors that may have shared functions in the biology of both retroviruses, as well as functions specific to RSV and HIV-1, given their distinctive hosts and molecular pathology. [ABSTRACT FROM AUTHOR]

The article outlines practical operational considerations for health-system pharmacy leaders when planning to onboard new gene therapy approvals. Topics discussed include site preparedness and biosafety recommendations, common gene therapy clinical and operational checklist, and importance of clinical practice guidelines for adverse effect management.

Background and Objectives Human lymphotropic virus type I mainly infects lymphocytes. For the detection of this virus, mainly nucleated cells are evaluated. Due to the short longevity of cells, sample collection is a challenge. The purpose of the study was to investigate the presence of HTLV-1 virus in genomic DNA released from cells in plasma and to determine its viral load in Western blotpositive blood donors Materials and Methods In this descriptive study, 30 HTLV-1 positive Western blot donors were evaluated. Using an extraction kit, genomic DNA was extracted from plasma and isolated PBMC using Ficol. A nested PCR test was used to confirm the presence of HTLV-1 virus. A real-time PCR quantitative test by Sybergreen method was used to determine the amount of virus load Results The average age of subjects was 42.9 ± 13.5 years; 93.3% of them were male and 6.6% female. LTR gene region was detected by nested PCR method in 80% of plasma and 100% of PBMC samples. The median viral loads in plasma and PBMC were 1.90 Copies/µL and 20 copies/106 PBMC, respectively. Conclusions To detect the HTLV-1 virus by molecular method, the HTLV-1 provirus DNA released from cells, in the plasma can be used when peripheral blood mononuclear cells are unavailable. It has also been observed that the virus load in the plasma of asymptomatic carriers is approximately 10 times lower than in PBMC. [ABSTRACT FROM AUTHOR]

Porcine endogenous retroviruses (PERVs) are integrated in the genome of all pigs. PERV-A, PERV-B and PERV-C can be released as infectious virus particles and PERV-A and PERV-B can infect human cells in culture. PERV-C does not infect human cells, but high-titer recombinant PERV-A/C can infect them. Retroviruses are able to induce immunosuppression and/or tumors in the infected host. Numerous methods have been developed to study PERV in donor pigs. No PERV infections were observed in infection experiments as well as in preclinical and clinical xenotransplantation trials. Despite this, several strategies have been developed to prevent PERV infection of the recipient. PCR-based and immunological methods are required to screen xenotransplant recipients. Since the proviruses are integrated into the pig genome, PERV infection has to be distinguished from microchimerism, e.g., the presence of pig cells in the recipient, which is common in xenotransplantation. Sensitive PCR methods using pig short interspersed nuclear elements (SINE) sequences allow to detect pig cells easily. Virus infection can also be detected by an increase of viral genomic or mRNA in human cells. The method of choice, however, is to screen for specific antibodies against PERV using different recombinant PERV proteins, purified viruses or peptides.

Endogenous retroviruses (ERVs) are traces of past viral infections commonly found in vertebrate genomes. Many ERVs are tightly regulated by the host genomes and co-opted for various functions within the hosts. Bats are the only true volant mammals, with the smallest mammalian genomes and a high fraction of ERVs within the genomes. They are important hosts for various zoonotic viral pathogens and can effectively modulate their immune response to tolerate viral infections. Integrations of retroviruses have been implicated as one of the mechanisms by which bats have co-evolved strategies to combat viral infections. In this study, we investigated the diversity of ERVs in over 40 publicly available bat genomes to understand the distribution and the evolution of ERVs within bats. We observed all classes of ERVs within bat genomes including even the complex lenti retroviruses. Alpha and spuma retroviruses which are generally considered rare in mammals, were common within bats. We observed a positive correlation between bat genome size and length of ERV elements. Interestingly, nearly 30 % of the ERVs within bats are intact suggesting a recent origin or co-option by the host genome. Future studies focusing on comparative genomic and experimental data will be critical to understand the role of these ERVs in host genome evolution.

Background: Human T-cell Leukemia Virus type-1 (HTLV-1) -associated myelopathy causes sufferers to experience changes in several aspects of their lives. Gaining a deeper understanding of these changes can help healthcare professionals improve care, enhance strategic decision-making, meet expectations, and manage patients effectively. However, there is no information about the experience and problems of patients with HTLV-1-associated myelopathy/tropical spastic paraparesis in Iran. Therefore, this study aimed to explain the lived experience of patients with HTLV-1-associated myelopathy/tropical spastic paraparesis. Methods: This qualitative study used hermeneutic phenomenology in 2022 in Mashhad, Iran. Participants were selected using purposeful sampling. Data were collected through 21 semi-structured in-depth interviews with 20 eligible patients with HTLV-1-associated myelopathy/tropical spastic paraparesis. The data were analyzed in MAXQDA/2020 using the six stages proposed by Van Manen. Results: The main concept of "Reduced self-sufficiency and social dignity" emerged from the narratives of the patients, which included three main categories: "Disruption of desirable personal and social life", "reduced perception of role competencies", and "obligatory unpleasant lifestyle changes". Conclusion: HTLV-1-associated myelopathy/tropical spastic paraparesis slowly makes patients feel insufficient and causes a sense of degradation in dignity. The disease can fundamentally change personal and social life. Thus, due to its incurability and progressiveness, palliative care should be provided to them to live with dignity. [ABSTRACT FROM AUTHOR]

Antiviral peptides (AVPs) have shown potential in inhibiting viral attachment, preventing viral fusion with host cells and disrupting viral replication due to their unique action mechanisms. They have now become a broad-spectrum, promising antiviral therapy. However, identifying effective AVPs is traditionally slow and costly. This study proposed a new two-stage computational framework for AVP identification. The first stage identifies AVPs from a wide range of peptides, and the second stage recognizes AVPs targeting specific families or viruses. This method integrates contrastive learning and multi-feature fusion strategy, focusing on sequence information and peptide characteristics, significantly enhancing predictive ability and interpretability. The evaluation results of the model show excellent performance, with accuracy of 0.9240 and Matthews correlation coefficient (MCC) score of 0.8482 on the non-AVP independent dataset, and accuracy of 0.9934 and MCC score of 0.9869 on the non-AMP independent dataset. Furthermore, our model can predict antiviral activities of AVPs against six key viral families (Coronaviridae, Retroviridae, Herpesviridae, Paramyxoviridae, Orthomyxoviridae, Flaviviridae) and eight viruses (FIV, HCV, HIV, HPIV3, HSV1, INFVA, RSV, SARS-CoV). Finally, to facilitate user accessibility, we built a user-friendly web interface deployed at https://awi.cuhk.edu.cn/∼dbAMP/AVP/. [ABSTRACT FROM AUTHOR]

The Covid-19 pandemic has shown how much of a global threat animal-borne viruses pose to human health and life. Despite increased hygiene practices, interspecies transmission of viruses can still occur. Pathogens undergo mutations, which makes it difficult to develop effective vaccines and targeted therapies. The tendency of viruses to mutate, their virulence and the ease of spreading in populations make it necessary to develop methods for neutralization and drugs against these pathogens. The paper presents an overview of substances effective in disinfecting surfaces contaminated with viruses transmitted by cats, such as feline immunodeficiency virus (FIV), feline leukaemia virus (FeLV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV -2) that may be transmitted by these animals. Ethanol, propanol, isopropanol, octenisept 4-phenoxyethanol, IV ammonium salts and mixtures of these substances effectively eliminate feline viruses. The article also discusses drugs used to treat infections and draws attention to misconceptions spread among cat owners. [ABSTRACT FROM AUTHOR]

The notion that viruses played a crucial role in the evolution of life is not a new concept. However, more recent insights suggest that this perception might be even more expansive, highlighting the ongoing impact of viruses on host evolution. Endogenous retroviruses (ERVs) are considered genomic remnants of ancient viral infections acquired throughout vertebrate evolution. Their exogenous counterparts once infected the host's germline cells, eventually leading to the permanent endogenization of their respective proviruses. The success of ERV colonization is evident so that it constitutes 8% of the human genome. Emerging genomic studies indicate that endogenous retroviruses are not merely remnants of past infections but rather play a corollary role, despite not fully understood, in host genetic regulation. This review presents some evidence supporting the crucial role of endogenous retroviruses in regulating host genetics. We explore the involvement of human ERVs (HERVs) in key physiological processes, from their precise and orchestrated activities during cellular differentiation and pluripotency to their contributions to aging and cellular senescence. Additionally, we discuss the costs associated with hosting a substantial amount of preserved viral genetic material. [ABSTRACT FROM AUTHOR]

The field of retroviral integration research has a long history that started with the provirus hypothesis and subsequent discoveries of the retroviral reverse transcriptase and integrase enzymes. Because both enzymes are essential for retroviral replication, they became valued targets in the effort to discover effective compounds to inhibit HIV-1 replication. In 2007, the first integrase strand transfer inhibitor was licensed for clinical use, and subsequently approved second-generation integrase inhibitors are now commonly co-formulated with reverse transcriptase inhibitors to treat people living with HIV. International meetings specifically focused on integrase and retroviral integration research first convened in 1995, and this paper is part of the Viruses Special Issue on the 7th International Conference on Retroviral Integration, which was held in Boulder Colorado in the summer of 2023. Herein, we overview key historical developments in the field, especially as they pertain to the development of the strand transfer inhibitor drug class. Starting from the mid-1990s, research advancements are presented through the lens of the international conferences. Our overview highlights the impact that regularly scheduled, subject-specific international meetings can have on community-building and, as a result, on field-specific collaborations and scientific advancements. [ABSTRACT FROM AUTHOR]

The epitranscriptomic modification m6A is a prevalent RNA modification that plays a crucial role in the regulation of various aspects of RNA metabolism. It has been found to be involved in a wide range of physiological processes and disease states. Of particular interest is the role of m6A machinery and modifications in viral infections, serving as an evolutionary marker for distinguishing between self and non-self entities. In this review article, we present a comprehensive overview of the epitranscriptomic modification m6A and its implications for the interplay between viruses and their host, focusing on immune responses and viral replication. We outline future research directions that highlight the role of m6A in viral nucleic acid recognition, initiation of antiviral immune responses, and modulation of antiviral signaling pathways. Additionally, we discuss the potential of m6A as a prognostic biomarker and a target for therapeutic interventions in viral infections. [ABSTRACT FROM AUTHOR]

DNA oncoviruses represent an intriguing subject due to their involvement in oncogenesis. These viruses have evolved mechanisms to manipulate the host immune response, facilitating their persistence and actively contributing to carcinogenic processes. This paper describes the complex interactions between DNA oncoviruses and the innate immune system, with a particular emphasis on the cGAS-STING pathway. Exploring these interactions highlights that DNA oncoviruses strategically target and subvert this pathway, exploiting its vulnerabilities for their own survival and proliferation within the host. Understanding these interactions lays the foundation for identifying potential therapeutic interventions. Herein, we sought to contribute to the ongoing efforts in advancing our understanding of the innate immune system in oncoviral pathogenesis. [ABSTRACT FROM AUTHOR]

PYHIN proteins are only found in mammals and play key roles in the defense against bacterial and viral pathogens. The corresponding gene locus shows variable deletion and expansion ranging from 0 genes in bats, over 1 in cows, and 4 in humans to a maximum of 13 in mice. While initially thought to act as cytosolic immune sensors that recognize foreign DNA, increasing evidence suggests that PYHIN proteins also inhibit viral pathogens by more direct mechanisms. Here, we examined the ability of all 13 murine PYHIN proteins to inhibit HIV-1 and murine leukemia virus (MLV). We show that overexpression of p203, p204, p205, p208, p209, p210, p211, and p212 strongly inhibits production of infectious HIV-1; p202, p207, and p213 had no significant effects, while p206 and p214 showed intermediate phenotypes. The inhibitory effects on infectious HIV-1 production correlated significantly with the suppression of reporter gene expression by a proviral Moloney MLV-eGFP construct and HIV-1 and Friend MLV LTR luciferase reporter constructs. Altogether, our data show that the antiretroviral activity of PYHIN proteins is conserved between men and mice and further support the key role of nuclear PYHIN proteins in innate antiviral immunity. [ABSTRACT FROM AUTHOR]

Aim: The present study examined the protective potential of human adipose tissue-derived mesenchymal stem cells (hASCs) modified to overexpress alpha-1 antitrypsin (AAT), in a mouse model of the liver fibrosis. Background: For the treatment of end-stage liver diseases, cell therapy has emerged as a promising noninvasive alternative to liver transplantation. Mesenchymal stem cells (MSCs) are being evaluated due to their dual capabilities of promoting liver regeneration and modulating the pathogenic inflammation of the immune system. Methods: Liver fibrosis was induced in mice via the intraperitoneal injection of carbon tetrachloride (CCl4). MSCs were extracted from the human adipose tissue. After stemness confirmation, the cells were transduced with the lentiviruses containing the AAT gene, and then injected into the mice's tail vein. Fourteen days' post-transplantation, mice were sacrificed, and blood and tissue samples were collected for analysis. Important liver enzymes, including alanine transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), albumin, and total bilirubin (TB), were measured. Histological studies were carried out using the hematoxylin and eosin (H&E), as well as Masson's trichrome (MT) staining. Results: Compared to hASCs, treatment with AAT-hASCs resulted in greater reductions in ALT, AST, ALP, and TB, as well as normalized albumin levels. AAT-hASCs promoted enhanced liver regeneration histologically, likely attributable to anti-inflammatory and anti-proteolytic properties of AAT. Conclusion: These findings indicate AAT-engineered hASCs as a promising cell-gene therapy candidate for further study in liver cirrhosis models. [ABSTRACT FROM AUTHOR]

Background: Both internal and external risk factors can accelerate the progression of breast cancer which is the reason why clinicians have tried to find new biomarkers for this health problem. Human endogenous retrovirus W (HERV W) can be one of these biomarkers, as it has been mentioned that some genes of this virus are able to have either higher or lower expression in numerous cancerous cells. In this study, we aimed to compare HERV W envelope expression in breast cancer tissues and normal ones since its effects on this malignancy have not been clear. Materials and Methods: We collected 46 breast cancer tissues and their normal adjacent ones. After extracting the RNA of breast samples, we evaluated the expression of HERV W envelope syncytin 1 and 2 using quantitative real time polymerase chain reaction (PCR) in different kinds of breast cancer stages. Results: Data showed that more than 13% of patients had a family history of breast cancer; moreover, approximately half of the tissues were estrogen receptor or progesterone receptor positive. Lymph node metastasis was seen in 52% of the patients, and about 40% of tumors were larger than 2 cm. Real time PCR showed that syncytin 1 and 2 had upward regulation with ( *P < 0.05) and (**P < 0.01), respectively. Conclusion: As the expression of HERV W Env (syncytin 1, syncytin 2) was higher in breast cancerous tissues in comparison with normal ones, we believe that these genes may have a role to play in monitoring patients suffering from this type of cancer. However, further studies are needed to confirm this hypothesis. [ABSTRACT FROM AUTHOR]

Host antiviral proteins inhibit primate lentiviruses and other retroviruses by targeting many features of the viral life cycle. The lentiviral capsid protein and the assembled viral core are known to be inhibited through multiple, directly acting antiviral proteins. Several phenotypes, including those known as Lv1 through Lv5, have been described as cell type-specific blocks to infection against some but not all primate lentiviruses. Here we review important features of known capsid-targeting blocks to infection together with several blocks to infection for which the genes responsible for the inhibition still remain to be identified. We outline the features of these blocks as well as how current methodologies are now well suited to find these antiviral genes and solve these long-standing mysteries in the HIV and retrovirology fields. [ABSTRACT FROM AUTHOR]

Approximately 15–20% of global cancer cases are attributed to virus infections. Oncoviruses employ various molecular strategies to enhance replication and persistence. Human cytomegalovirus (HCMV), acting as an initiator or promoter, enables immune evasion, supporting tumor growth. HCMV activates pro-oncogenic pathways within infected cells and direct cellular transformation. Thus, HCMV demonstrates characteristics reminiscent of oncoviruses. Cumulative evidence emphasizes the crucial roles of EZH2 and Myc in oncogenesis and stemness. EZH2 and Myc, pivotal regulators of cellular processes, gain significance in the context of oncoviruses and HCMV infections. This axis becomes a central focus for comprehending the mechanisms driving virus-induced oncogenesis. Elevated EZH2 expression is evident in various cancers, making it a prospective target for cancer therapy. On the other hand, Myc, deregulated in over 50% of human cancers, serves as a potent transcription factor governing cellular processes and contributing to tumorigenesis; Myc activates EZH2 expression and induces global gene expression. The Myc/EZH2 axis plays a critical role in promoting tumor growth in oncoviruses. Considering that HCMV has been shown to manipulate the Myc/EZH2 axis, there is emerging evidence suggesting that HCMV could be regarded as a potential oncovirus due to its ability to exploit this critical pathway implicated in tumorigenesis. [ABSTRACT FROM AUTHOR]

Microglia are resident immune cells in the central nervous system (CNS) that play vital roles in CNS development, homeostasis and disease pathogenesis. Genetic defects in microglia lead to microglial dysfunction, which in turn leads to neurological disorders. The correction of the specific genetic defects in microglia in these disorders can lead to therapeutic effects. Traditional genetic defect correction approaches are dependent on viral vectorbased genetic defect corrections. However, the viruses used in these approaches, including adeno-associated viruses, lentiviruses and retroviruses, do not primarily target microglia; therefore, viral vector-based genetic defect corrections are ineffective in microglia. Microglia replacement is a novel approach to correct microglial genetic defects via replacing microglia of genetic defects with allogenic healthy microglia. In this paper, we systematically review the history, rationale and therapeutic perspectives of microglia replacement, which would be a novel strategy for treating CNS disorders. [ABSTRACT FROM AUTHOR]

Human astrovirus (HAstV) is a nonenveloped RNA virus and has been implicated in acute gastroenteritis among children and elderly. However, there exists a substantial dearth of information on HAstV strains circulating in Nigeria. Viral‐like particles were purified from archived 254 stool samples of children with acute flaccid paralysis between January and December 2020 from five states in Nigeria, using the NetoVIR protocol. Extracted viral RNA and DNA were subjected to a reverse transcription step and subsequent random polymerase chain reaction amplification. Library preparation and Illumina sequencing were performed. Using the virome paired‐end reads pipeline, raw reads were processed into genomic contigs. Phylogenetic and pairwise identity analysis of the recovered HAstV genomes was performed. Six near‐complete genome sequences of HAstV were identified and classified as HAstV4 (n = 1), HAstV5 (n = 1), HAstV8 (n = 1), and MLB‐3 (n = 3). The HAstV5 belonged to a yet unclassified sublineage, which we tentatively named HAstV‐5d. Phylogenetic analysis of open reading frames 1a, 1b, and 2 suggested recombination events inside the MAstV1 species. Furthermore, phylogenetic analysis implied a geographic linkage between the HAstV5 strain from this study with two strains from Cameroon across all the genomic regions. We report for the first time the circulation of HAstV genotypes 4, 8, and MLB‐3 in Nigeria and present data suggestive for the existence of a new sublineage of HAstV5. To further understand the burden, diversity, and evolution of HAstV, increased research interest as well as robust HAstV surveillance in Nigeria is essential. [ABSTRACT FROM AUTHOR]

ABSTRACT We have investigated the function of inositol hexakisphosphate (IP6) and inositol pentakisphosphate (IP5) in the replication of murine leukemia virus (MLV). While IP6 is known to be critical for the life cycle of HIV-1, its significance in MLV remains unexplored. We find that IP6 is indeed important for MLV replication. It significantly enhances endogenous reverse transcription (ERT) in MLV. Additionally, a pelleting-based assay reveals that IP6 can stabilize MLV cores, thereby facilitating ERT. We find that IP5 and IP6 are packaged in MLV particles. However, unlike HIV-1, MLV depends upon the presence of IP6 and IP5 in target cells for successful infection. This IP6/5 requirement for infection is reflected in impaired reverse transcription observed in IP6/5-deficient cell lines. In summary, our findings demonstrate the importance of capsid stabilization by IP6/5 in the replication of diverse retroviruses; we suggest possible reasons for the differences from HIV-1 that we observed in MLV.IMPORTANCEInositol hexakisphosphate (IP6) is crucial for the assembly and replication of HIV-1. IP6 is packaged in HIV-1 particles and stabilizes the viral core enabling it to synthesize viral DNA early in viral infection. While its importance for HIV-1 is well established, its significance for other retroviruses is unknown. Here we report the role of IP6 in the gammaretrovirus, murine leukemia virus (MLV). We found that like HIV-1, MLV packages IP6, and as in HIV-1, IP6 stabilizes the MLV core thus promoting reverse transcription. Interestingly, we discovered a key difference in the role of IP6 in MLV versus HIV-1: while HIV-1 is not dependent upon IP6 levels in target cells, MLV replication is significantly reduced in IP6-deficient cell lines. We suggest that this difference in IP6 requirements reflects key differences between HIV-1 and MLV replication.

The efficiency of human immunodeficiency virus-1 (HIV-1) inhibition by sulfated polysaccharides isolated from the various families of red algae of the Far East Pacific coast were studied. The anti-HIV-1 activity of kappa and lambda-carrageenans from Chondrus armatus, original highly sulfated X-carrageenan with low content of 3,6-anhydrogalactose from Tichocarpus crinitus and i/κ–carrageenan with hybrid structure isolated from Ahnfeltiopsis flabelliformis was found. The antiviral action of these polysaccharides and its low-weight oligosaccharide was compared with commercial κ-carrageenan. Here we used the HIV-1-based lentiviral particles and evaluated that these carrageenans in non-toxic concentrations significantly suppress the transduction potential of lentiviral particles pseudotyped with different envelope proteins, targeting cells of neuronal or T-cell origin. The antiviral action of these carrageenans was confirmed using the chimeric replication competent Mo-MuLV (Moloney murine leukemia retrovirus) encoding marker eGFP protein. We found that X-carrageenans from T. crinitus and its low weight derivative and λ-carrageenan from C. armatus effectively suppress the infection caused by retrovirus. The obtained data suggest that the differences in the suppressive effect of carrageenans on the transduction efficiency of HIV-1 based lentiviral particles may be related to the structural features of the studied polysaccharides.

Microbial eukaryotes, giant viruses and virophages form a unique hyperparasitic system. Virophages are parasites of the virus transcription machinery and can interfere with virus replication, resulting in a benefit to the eukaryotic host population. Surprisingly, virophages can integrate into the genomes of their cell or virus hosts, and have been shown to reactivate during coinfection. This raises questions about the role of integration in the dynamics of cell-virus-virophage systems. We use mathematical models and computational simulations to understand the effect of virophage integration on populations of cells and viruses. We also investigate multicellularity and programmed cell-death (PCD) as potential antiviral defence strategies used by cells. We found that virophages which enter the cell independently of the host virus, such as Mavirus, are expected to integrate commonly into the genomes of their cell hosts. Our models suggest that integrations from virophages without an independent mode of entry like Sputnik, are less likely to become fixed in the cell host population. Alternatively, we found that Sputnik virophages can stably persist integrated in the virus population, as long as they do not completely inhibit virus replication. We also show that increasing virophage inhibition can stabilise oscillatory dynamics, which may explain the long-term persistence of viruses and virophages in the environment. Our results demonstrate that inhibition by virophages and multicellularity are effective antiviral strategies that may act in synergy against viral infection in microbial species. Author summary: Giant viruses can be infected by their own viruses called virophages ('virus eater'). Together with microbial eukaryotes, giant viruses and virophages form a unique parasitic system. Recently, virophages were discovered to become part of the genome of their host eukaryote or giant virus (a process called integration). We used mathematical models and simulations to explore how populations of cells, viruses and virophages interact in the presence of integration. We found that inhibition of virus replication by virophages can lead to stable interactions, and that cells and viruses carrying a virophage can become firmly established in the population, even when there is no direct advantage to the host. Computational simulations also indicated that inhibition by virophages and multicellularity can be protective for the cell population. Given that giant viruses and virophages seem to be at least as old as the early eukaryotes, our results could provide insights into the antiviral strategies used by ancient eukaryotic organisms. [ABSTRACT FROM AUTHOR]

Understanding the local epidemiology of feline leukaemia virus (FeLV) and feline immunodeficiency virus (FIV) in Hong Kong will inform retrovirus prevention strategies. Domestic cat hepadnavirus (DCH), a novel hepatitis-B-like virus, is commonly detected among client-owned cats in Hong Kong, but community cats have not been studied. The aims of this study were to investigate the frequency and potential risk factors for (i) FeLV and FIV among community and client-owned cats and (ii) perform molecular detection of DCH among community cats in Hong Kong. Blood samples from 713 cats were obtained from client-owned (n = 415, residual diagnostic) and community cats (n = 298, at trap-neuter-return). Point-of-care (POC) testing for FeLV antigen and feline immunodeficiency virus (FIV) anti-p15 and p24 antibodies was performed. FeLV-positive samples were progressed to p27 sandwich enzyme-linked immunosorbent assay. Whole blood DNA was tested with qPCRs for FeLV U3 and gag, and nested PCRs where additional information was required. DCH qPCR was performed on a subset of community cats (n = 193). A single, regressive, FeLV infection was detected in a client-owned cat (1/415 FeLV U3 qPCR positive, 0.2%, 95% CI 0.0–1.3%). Five/415 client-owned cats tested presumably false FeLV-antigen positive (qPCR negative). No markers of FeLV infection were detected in community cats (0/298; 0%). FIV seroprevalence was much higher in community cats (46/298, 15.4%) than in client-owned cats (13/415, 3.1%) (p < 0.001). Mixed breed was a risk factor for FIV infection in client-owned cats. Neither sex nor age were associated with FIV infection. DCH DNA was detected in 34/193 (17.6%) community cats (median viral load 6.32 × 103 copies/reaction). FeLV infection is rare in Hong Kong, negatively impacting the positive predictive value of diagnostic tests. FeLV-antigen testing remains the screening test of choice, but confirmation of a positive result using FeLV qPCR is essential. FIV infection is common in community cats and the absence of a sex predisposition, seen previously in cats managed similarly, raises questions about virus-transmission dynamics in these groups. DCH infection is very common in Hong Kong, both in client-owned and community cats, highlighting the importance of understanding the pathogenic potential of this virus for cats. [ABSTRACT FROM AUTHOR]

Interindividual variability in drug response is a major problem in the prescription of pharmacological treatments. The therapeutic effect of drugs can be influenced by human genes. Pharmacogenomic guidelines for individualization of treatment have been validated and used for conventional dosage forms. However, drugs can often target non-specific areas and produce both desired and undesired pharmacological effects. The use of nanoparticles, liposomes, or other available forms for drug formulation could help to overcome the latter problem. Virus-like particles based on retroviruses could be a potential envelope for safe and efficient drug formulations. Human endogenous retroviruses would make it possible to overcome the host immune response and deliver drugs to the desired target. PEG10 is a promising candidate that can bind to mRNA because it is secreted like an enveloped virus-like extracellular vesicle. PEG10 is a retrotransposon-derived gene that has been domesticated. Therefore, formulations with PEG10 may have a lower immunogenicity. The use of existing knowledge can lead to the development of suitable drug formulations for the precise treatment of individual diseases. [ABSTRACT FROM AUTHOR]

This document discusses the use of haploidentical peripheral blood stem cell transplantation (haplo-HSCT) as a treatment for adult T-cell leukemia/lymphoma (ATL), a type of peripheral T-cell lymphoma caused by human T-cell leukemia virus type I (HTLV-1). The study examines the clonality patterns of HTLV-1-infected cells in five patients who underwent haplo-HSCT using a novel method called Rapid Amplification of Integration Sites without Interference by Genomic DNA contamination (RAISING). The results show that the clonality and proliferation of HTLV-1-infected cells after haplo-HSCT are heterogeneous, and RAISING is a cost-effective and time-saving method to evaluate the clonality of these cells. Further research is needed to establish a monitoring system for the accurate and early diagnosis of ATL after HSCT. [Extracted from the article]

Feline leukemia virus (FeLV) is an exogenous retrovirus that causes malignant hematopoietic disorders in domestic cats, and its virulence may be closely associated with viral sequences. FeLV is classified into several subgroups, including A, B, C, D, E, and T, based on viral receptor interference properties or receptor usage. However, the transmission manner and disease specificity of the recombinant viruses FeLV-D and FeLV-B remain unclear. The aim of this study was to understand recombination events between exogenous and endogenous retroviruses within a host and elucidate the emergence and transmission of recombinant viruses. We observed multiple recombination events involving endogenous retroviruses (ERVs) in FeLV from a family of domestic cats kept in one house; two of these cats (ON-T and ON-C) presented with lymphoma and leukemia, respectively. Clonal integration of FeLV-D was observed in the ON-T case, suggesting an association with FeLV-D pathogenesis. Notably, the receptor usage of FeLV-B observed in ON-T was mediated by feline Pit1 and feline Pit2, whereas only feline Pit1 was used in ON-C. Furthermore, XR-FeLV, a recombinant FeLV containing an unrelated sequence referred to the X-region, which is homologous to a portion of the 5′-leader sequence of Felis catus endogenous gammaretrovirus 4 (FcERV-gamma4), was isolated. Genetic analysis suggested that most recombinant viruses occurred de novo; however, the possibility of FeLV-B transmission was also recognized in the family. This study demonstrated the occurrence of multiple recombination events between exogenous and endogenous retroviruses in domestic cats, highlighting the contribution of ERVs to pathogenic recombinant viruses. IMPORTANCE Feline leukemia virus subgroup A (FeLV-A) is primarily transmitted among cats. During viral transmission, genetic changes in the viral genome lead to the emergence of novel FeLV subgroups or variants with altered virulence. We isolated three FeLV subgroups (A, B, and D) and XR-FeLV from two cats and identified multiple recombination events in feline endogenous retroviruses (ERVs), such as enFeLV, ERV-DC, and FcERV-gamma4, which are present in the cat genome. This study highlights the pathogenic contribution of ERVs in the emergence of FeLV-B, FeLV-D, and XR-FeLV in a feline population. [ABSTRACT FROM AUTHOR]

Viruses that carry a positive-sense, single-stranded (+ssRNA) RNA translate their genomes soon after entering the host cell to produce viral proteins, with the exception of retroviruses. A distinguishing feature of retroviruses is reverse transcription, where the +ssRNA genome serves as a template to synthesize a double-stranded DNA copy that subsequently integrates into the host genome. As retroviral RNAs are produced by the host cell transcriptional machinery and are largely indistinguishable from cellular mRNAs, we investigated the potential of incoming retroviral genomes to directly express proteins. Here we show through multiple, complementary methods that retroviral genomes are translated after entry. Our findings challenge the notion that retroviruses require reverse transcription to produce viral proteins. Synthesis of retroviral proteins in the absence of productive infection has significant implications for basic retrovirology, immune responses and gene therapy applications. A defining feature of retroviruses compared to other +ssRNA viruses is reverse transcription. Here, Köppke et al. show that retroviruses (e.g. HIV-1) can produce viral proteins even in the absence of reverse transcription. [ABSTRACT FROM AUTHOR]

Cat ownership is common in Chile, but data on the regional prevalence of infectious agents are limited. A sero-molecular survey of 120 client- or shelter-owned domestic cats in greater Santiago was performed. Whole blood DNA was tested for the novel hepatitis-B-like virus, domestic cat hepadnavirus (DCH) by conventional PCR (cPCR) and quantitative PCR (qPCR), and for feline leukaemia virus (FeLV) by qPCR. Point-of-care serology for FeLV p27 antigen and antibodies recognising feline immunodeficiency virus (FIV) p15 and p24 was performed. DCH DNA was detected in the serum of 2/120 cats (1.67%). Sequencing and phylogenetic analysis showed that the DCH detected in Chile occupies a position outside the main clustering of DCH in the near-complete genome tree. Progressive (antigen-positive, provirus-positive) and regressive (antigen-negative, provirus-positive) FeLV infections were identified in 6/120 (5%) and 9/120 (7.5%) of cats. A total of 2/120 (1.7%) cats had dual FeLV/FIV infection, and another 2 cats had FIV infection alone. This study shows that the global footprint of DCH includes South America with a low molecular frequency in Chile, similar to that reported in the USA. Progressive FeLV infection is relatively common in urban Chile, and male cats are at greater risk than females. Testing and control measures for pathogenic retroviruses are indicated. The potential impact of FeLV, FIV and DCH on Chile's wildcat species is worthy of further investigation. [ABSTRACT FROM AUTHOR]