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Aims: To evaluate whether antibodies specific for the vaccinia virus (VV) are still detectable after at least 45 years from immunization. To confirm that VV-specific antibodies are endowed with the capacity to neutralize Mpox virus (MPXV) in vitro. To test a possible role of polyclonal non-specific activation in the maintenance of immunologic memory. Methods: Sera were collected from the following groups: smallpox-vaccinated individuals with or without latent tuberculosis infection (LTBI), unvaccinated donors, and convalescent individuals after MPXV infection. Supernatant of VV- or MPXV-infected Vero cells were inactivated and used as antigens in ELISA or in Western blot (WB) analyses. An MPXV plaque reduction neutralization test (PRNT) was optimized and performed on study samples. VV- and PPD-specific memory T cells were measured by flow cytometry. Results: None of the smallpox unvaccinated donors tested positive in ELISA or WB analysis and their sera were unable to neutralize MPXV in vitro. Sera from all the individuals convalescing from an MPXV infection tested positive for anti-VV or MPXV IgG with high titers and showed MPXV in vitro neutralization capacity. Sera from most of the vaccinated individuals showed IgG anti-VV and anti-MPXV at high titers. WB analyses showed that positive sera from vaccinated or convalescent individuals recognized both VV and MPXV antigens. Higher VV-specific IgG titer and specific T cells were observed in LTBI individuals. Conclusions: ELISA and WB performed using supernatant of VV- or MPXV-infected cells are suitable to identify individuals vaccinated against smallpox at more than 45 years from immunization and individuals convalescing from a recent MPXV infection. ELISA and WB results show a good correlation with PRNT. Data confirm that a smallpox vaccination induces a long-lasting memory in terms of specific IgG and that antibodies raised against VV may neutralize MPXV in vitro. Finally, higher titers of VV-specific antibodies and higher frequency of VV-specific memory T cells in LTBI individuals suggest a role of polyclonal non-specific activation in the maintenance of immunologic memory. [ABSTRACT FROM AUTHOR]

The frequency of locally transmitted dengue virus (DENV) infections has increased in Europe in recent years, facilitated by the invasive mosquito species Aedes albopictus, which is well established in a large area of Europe. In Italy, the first indigenous dengue outbreak was reported in August 2020 with 11 locally acquired cases in the Veneto region (northeast Italy), caused by a DENV-1 viral strain closely related to a previously described strain circulating in Singapore and China. In this study, we evaluated the vector competence of two Italian populations of Ae. albopictus compared to an Ae. aegypti lab colony. We performed experimental infections using a DENV-1 strain that is phylogenetically close to the strain responsible for the 2020 Italian autochthonous outbreak. Our results showed that local Ae. albopictus is susceptible to infection and is able to transmit the virus, confirming the relevant risk of possible outbreaks starting from an imported case. [ABSTRACT FROM AUTHOR]

Dengue (DENV) and Zika (ZIKV) viruses are mosquito-borne human pathogens. In Italy, the presence of the competent vector Aedes albopictus increases the risk of autochthonous transmission, and a national plan for arboviruses prevention, surveillance, and response (PNA 2020–2025) is in place. The results of laboratory diagnosis of both viruses by the National Reference Laboratory for arboviruses (NRLA) from November 2015 to November 2022 are presented. Samples from 655 suspected cases were tested by both molecular and serological assays. Virus and antibody kinetics, cross-reactivity, and diagnostic performance of IgM ELISA systems were analysed. Of 524 cases tested for DENV, 146 were classified as confirmed, 7 as probable, while 371 were excluded. Of 619 cases tested for ZIKV, 44 were classified as confirmed, while 492 were excluded. All cases were imported. Overall, 75.3% (110/146) of DENV and 50% (22/44) of ZIKV cases were confirmed through direct virus detection methods. High percentages of cross reactivity were observed between the two viruses. The median lag time from symptoms onset to sample collection was 7 days for both DENV molecular (range 0–20) and NS1 ELISA (range 0–48) tests, with high percentages of positivity also after 7 days (39% and 67%, respectively). For ZIKV, the median lag time was 5 days (range 0–22), with 16% positivity after 7 days. Diagnostic performance was assessed with negative predictive values ranging from 92% to 95% for the anti-DENV systems, and of 97% for the ZIKV one. Lower positive predictive values were seen in the tested population (DENV: 55% to 91%, ZIKV: 50%). DENV and ZIKV diagnosis by molecular test is the gold standard, but sample collection time is a limitation. Serological tests, including Plaque Reduction Neutralization Test, are thus necessary. Co-circulation and cross-reactivity between the two viruses increase diagnostic difficulty. Continuous evaluation of diagnostic strategies is essential to improve laboratory testing. [ABSTRACT FROM AUTHOR]

There is an urgent need to identify efficient antiviral compounds to combat existing and emerging RNA virus infections, particularly those related to seasonal and pandemic influenza outbreaks. While inhibitors of the influenza viral integral membrane proton channel protein (M2), neuraminidase (NA), and cap-dependent endonuclease are available, circulating influenza viruses acquire resistance over time. Thus, the need for the development of additional anti-influenza drugs with novel mechanisms of action exists. In the present study, a cell-based screening assay and a small molecule library were used to screen for activities that antagonized influenza A non-structural protein 1 (NS1), a highly conserved, multifunctional accessory protein that inhibits the type I interferon response against influenza. Two potential anti-influenza agents, compounds 157 and 164, were identified with anti-NS1 activity, resulting in the reduction of A/PR/8/34(H1N1) influenza A virus replication and the restoration of IFN-β expression in human lung epithelial A549 cells. A 3D pharmacophore modeling study of the active compounds provided a glimpse of the structural motifs that may contribute to anti-influenza virus activity. This screening approach is amenable to a broader analysis of small molecule compounds to inhibit other viral targets. [ABSTRACT FROM AUTHOR]

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Masons' marks can be seen as informative symbols designed to convey one or more pieces of information from stonemasons or officials to other actors involved in the carving and building process. As such, when evaluated in their respective archaeological contexts, they can shed light on the artisanal and technical dynamics at play at different stages of work on building sites. In Late Antiquity, the alphabetic characters, usually carved on stone elements only once, had the form of single letters, multiple letters in ligature, or monograms. However, the marked objects were often double-numbered or, more rarely, engraved with multiple groups of marks. A thorough study of this phenomenon aims to explain the function of these marks and their significance for the workflow. In some cases, assembly or positioning marks are coupled with workshop marks, indicating the need of different groups of craftsmen to convey specific technical information. In other cases, more than one workshop is recorded on a single piece, providing data on the complexity of the craftsmanship, on the labor effort involved, and thus on the economic dimension of the project. This paper attempts to reassess the phenomenon of multiple masons' marks in its historical and geographical dimensions, with a focus on the building sites of the imperial capital and further reference to other archaeological examples throughout the Mediterranean. [ABSTRACT FROM AUTHOR]

This document is a special issue of the journal "Viruses" focused on arbovirus diagnostics. Arboviruses are pathogens transmitted by mosquitoes, ticks, and sandflies, and accurate diagnostic strategies are crucial for public health. The articles in this issue cover a range of topics, including the need for comprehensive diagnostics during the chikungunya virus epidemic in Myanmar, the importance of surveillance programs for chikungunya virus in Vietnam, the challenges of differential diagnosis for arboviruses with overlapping symptoms, and innovative approaches to arbovirus detection using non-invasive samples. Other articles explore vaccine development, improved detection methods for specific arboviruses, and advanced genomic surveillance for West Nile virus. The authors emphasize the importance of continued research and innovation in arbovirus diagnostics to mitigate the impact of these complex pathogens on global health. [Extracted from the article]

Several flaviviruses such as Hepatitis C virus, West Nile virus, Dengue virus and Japanese Encephalitis virus exploit the raft platform to enter host cells whereas the involvement of lipid rafts in Zika virus–host cell interaction has not yet been demonstrated. Zika virus disease is caused by a flavivirus transmitted by Aedes spp. Mosquitoes, although other mechanisms such as blood transfusion, sexual and maternal–fetal transmission have been demonstrated. Symptoms are generally mild, such as fever, rash, joint pain and conjunctivitis, but neurological complications, including Guillain-Barré syndrome, have been associated to this viral infection. During pregnancy, it can cause microcephaly and other congenital abnormalities in the fetus, as well as pregnancy complications, representing a serious health threat. In this study, we show for the first time that Zika virus employs cell membrane lipid rafts as a portal of entry into Vero cells. We previously demonstrated that the antifungal drug Amphotericin B (AmphB) hampers a microbe–host cell interaction through the disruption of lipid raft architecture. Here, we found that Amphotericin B by the same mechanism of action inhibits both Zika virus cell entry and replication. These data encourage further studies on the off-label use of Amphotericin B in Zika virus infections as a new and alternate antiviral therapy. [ABSTRACT FROM AUTHOR]

Background: The latest European Chikungunya virus (CHIKV) outbreak occurred in Italy in 2017, in the municipalities of Anzio and Rome (Lazio Region), with a secondary outbreak in the Calabrian Region. Most CHIKV infections are symptomatic but about 15% of people who acquire the infection may be asymptomatic. A retrospective study was conducted with the aim of assessing the prevalence of recent/ongoing CHIKV infections on the blood donor population in the Lazio Region, during the 2017 outbreak (including in the period before it was detected). Methods: The study was conducted on 4595 plasma samples from donors who donated in 14 different Blood Establishments in the Lazio Region, in the period June–November 2017. A total of 389 of these samples were collected in provinces not affected by the outbreak and were used as negative controls. All samples were tested for IgM detection by the use of an ELISA test, and positive samples were tested for confirmation through the use of a PRNT. Molecular tests were performed on sera that were found to be IgM-positive or borderline. Results: A total of 41 (0.89%) blood donors tested positive for IgM. None of these positive IgM ELISA results was confirmed either by PRNT or by molecular tests. Conclusions: Our study has shown no evidence of recent/ongoing CHIKV infection in blood donors of the affected area. [ABSTRACT FROM AUTHOR]

Background: On 11 March 2020, the World Health Organisation (WHO) declared the coronavirus disease 2019 (COVID-19) outbreak to be a pandemic. As the mosquito season progressed, the understandable concern that mosquitoes could transmit the virus began to increase among the general public and public health organisations. We have investigated the vector competence of Culex pipiens and Aedes albopictus, the two most common species of vector mosquitoes in Europe, for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Due to the very unusual feeding behaviour of Ae. albopictus, we also evaluated the role of this mosquito in a potential mechanical transmission of the virus. Methods: For the vector competence study, mosquitoes were allowed to take several infectious blood meals. The mosquitoes were then collected and analysed at 0, 3, 7 and 10 days post-feeding. For the mechanical transmission test, Ae. albopictus females were allowed to feed for a short time on a feeder containing infectious blood and then on a feeder containing virus-free blood. Both mosquitoes and blood were tested for viral presence. Results: Culex pipiens and Ae. albopictus were found not be competent vectors for SARS-CoV-2, and Ae. albopictus was unable to mechanically transmit the virus. Conclusions: This is the first study to show that the most common species of vector mosquitoes in Europe do not transmit SARS-CoV-2 and that Ae. albopictus is unable to mechanically transmit the virus from a positive host to a healthy host through host-feeding. [ABSTRACT FROM AUTHOR]

Background: Pandemic coronavirus disease 2019 (COVID-19) disease represents a challenge for healthcare structures. The molecular confirmation of samples from infected individuals is crucial and therefore guides public health decision making. Clusters and possibly increased diffuse transmission could occur in the context of the next influenza season. For this reason, a diagnostic test able to discriminate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from influenza viruses is urgently needed.Methods: A multiplex real-time reverse-transcription polymerase chain reaction (PCR) assay was assessed using 1 laboratory protocol with different real-time PCR instruments. Overall, 1000 clinical samples (600 from samples SARS-CoV-2-infected patients, 200 samples from influenza-infected patients, and 200 negative samples) were analyzed.Results: The assay developed was able to detect and discriminate each virus target and to intercept coinfections. The limit of quantification of each assay ranged between 5 and 10 genomic copy numbers, with a cutoff value of 37.7 and 37.8 for influenza and SARS-CoV-2 viruses, respectively. Only 2 influenza coinfections were detected in COVID-19 samples.Conclusions: This study suggests that multiplex assay is a rapid, valid, and accurate method for the detection of SARS-CoV-2 and influenza viruses in clinical samples. The test may be an important diagnostic tool for both diagnostic and surveillance purposes during the seasonal influenza activity period. [ABSTRACT FROM AUTHOR]

Background: On 11 March 2020, the World Health Organisation (WHO) declared the coronavirus disease 2019 (COVID-19) outbreak to be a pandemic. As the mosquito season progressed, the understandable concern that mosquitoes could transmit the virus began to increase among the general public and public health organisations. We have investigated the vector competence of Culex pipiens and Aedes albopictus, the two most common species of vector mosquitoes in Europe, for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Due to the very unusual feeding behaviour of Ae. albopictus, we also evaluated the role of this mosquito in a potential mechanical transmission of the virus. Methods: For the vector competence study, mosquitoes were allowed to take several infectious blood meals. The mosquitoes were then collected and analysed at 0, 3, 7 and 10 days post-feeding. For the mechanical transmission test, Ae. albopictus females were allowed to feed for a short time on a feeder containing infectious blood and then on a feeder containing virus-free blood. Both mosquitoes and blood were tested for viral presence. Results: Culex pipiens and Ae. albopictus were found not be competent vectors for SARS-CoV-2, and Ae. albopictus was unable to mechanically transmit the virus. Conclusions: This is the first study to show that the most common species of vector mosquitoes in Europe do not transmit SARS-CoV-2 and that Ae. albopictus is unable to mechanically transmit the virus from a positive host to a healthy host through host-feeding. [ABSTRACT FROM AUTHOR]

Background: On 11 March 2020, the World Health Organisation (WHO) declared the coronavirus disease 2019 (COVID-19) outbreak to be a pandemic. As the mosquito season progressed, the understandable concern that mosquitoes could transmit the virus began to increase among the general public and public health organisations. We have investigated the vector competence of Culex pipiens and Aedes albopictus, the two most common species of vector mosquitoes in Europe, for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Due to the very unusual feeding behaviour of Ae. albopictus, we also evaluated the role of this mosquito in a potential mechanical transmission of the virus. Methods: For the vector competence study, mosquitoes were allowed to take several infectious blood meals. The mosquitoes were then collected and analysed at 0, 3, 7 and 10 days post-feeding. For the mechanical transmission test, Ae. albopictus females were allowed to feed for a short time on a feeder containing infectious blood and then on a feeder containing virus-free blood. Both mosquitoes and blood were tested for viral presence. Results: Culex pipiens and Ae. albopictus were found not be competent vectors for SARS-CoV-2, and Ae. albopictus was unable to mechanically transmit the virus. Conclusions: This is the first study to show that the most common species of vector mosquitoes in Europe do not transmit SARS-CoV-2 and that Ae. albopictus is unable to mechanically transmit the virus from a positive host to a healthy host through host-feeding. [ABSTRACT FROM AUTHOR]

Background: On 11 March 2020, the World Health Organisation (WHO) declared the coronavirus disease 2019 (COVID-19) outbreak to be a pandemic. As the mosquito season progressed, the understandable concern that mosquitoes could transmit the virus began to increase among the general public and public health organisations. We have investigated the vector competence of Culex pipiens and Aedes albopictus, the two most common species of vector mosquitoes in Europe, for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Due to the very unusual feeding behaviour of Ae. albopictus, we also evaluated the role of this mosquito in a potential mechanical transmission of the virus. Methods: For the vector competence study, mosquitoes were allowed to take several infectious blood meals. The mosquitoes were then collected and analysed at 0, 3, 7 and 10 days post-feeding. For the mechanical transmission test, Ae. albopictus females were allowed to feed for a short time on a feeder containing infectious blood and then on a feeder containing virus-free blood. Both mosquitoes and blood were tested for viral presence. Results: Culex pipiens and Ae. albopictus were found not be competent vectors for SARS-CoV-2, and Ae. albopictus was unable to mechanically transmit the virus. Conclusions: This is the first study to show that the most common species of vector mosquitoes in Europe do not transmit SARS-CoV-2 and that Ae. albopictus is unable to mechanically transmit the virus from a positive host to a healthy host through host-feeding. [ABSTRACT FROM AUTHOR]

The interferon regulatory factor (IRF) family consists of transcriptional regulators that exert multifaceted and versatile functions in multiple biological processes. Their crucial role as central mediators in the establishment and execution of host immunity in response to pathogen-derived signals downstream pattern recognition receptors (PRRs) makes IRFs a hallmark of the host antiviral response. They function as hub molecules at the crossroad of different signaling pathways for the induction of interferon (IFN) and inflammatory cytokines, as well as of antiviral and immunomodulatory genes even in an IFN-independent manner. By regulating the development and activity of immune cells, IRFs also function as a bridge between innate and adaptive responses. As such, IRFs represent attractive and compulsive targets in viral strategies to subvert antiviral signaling. In this study, we discuss current knowledge on the wide array of strategies put in place by pathogenic viruses to evade, subvert, and/or hijack these essential components of host antiviral immunity. [ABSTRACT FROM AUTHOR]

IκB kinase ε (IKK-ε) has an essential role as a regulator of innate immunity, functioning downstream of pattern recognition receptors to modulate NF-κB and interferon (IFN) signaling. In the present study, we investigated IKK-ε activation following T cell receptor (TCR)/CD28 stimulation of primary CD4+ T cells and its role in the stimulation of a type I IFN response. IKK-ε was activated following TCR/CD28 stimulation of primary CD4+ T cells; however, in T cells treated with poly(I·C), TCR/CD28 costimulation blocked induction of IFN-β transcription. We demonstrated that IKK-ε phosphorylated the transcription factor IFN regulatory factor 1 (IRF-1) at amino acid (aa) 215/219/221 in primary CD4+ T cells and blocked its transcriptional activity. At the mechanistic level, IRF-1 phosphorylation impaired the physical interaction between IRF-1 and the NF-κB RelA subunit and interfered with PCAF-mediated acetylation of NF-κB RelA. These results demonstrate that TCR/CD28 stimulation of primary T cells stimulates IKK-ε activation, which in turn contributes to suppression of IFN-β production. [ABSTRACT FROM AUTHOR]

Motivation: There is an urgent need for new medications to combat influenza pandemics.Methods: Using the genome analysis of the influenza A virus performed previously, we designed and performed a combinatorial exhaustive systematic methodology for optimal design of universal therapeutic small interfering RNA molecules (siRNAs) targeting all diverse influenza A viral strains. The rationale was to integrate the factors for highly efficient design in a pipeline of analysis performed on possible influenza-targeting siRNAs. This analysis selects specific siRNAs that has the ability to target highly conserved, accessible and biologically significant regions. This would require minimal dosage and side effects.Results and Discussion: First, >6000 possible siRNAs were designed. Successive filtration followed where a novel method for siRNA scoring filtration layers was implemented. This method excluded siRNAs below the 90% experimental inhibition mapped scores using the intersection of 12 different scoring algorithms. Further filtration of siRNAs is done by eliminating those with off-targets in the human genome and those with undesirable properties and selecting siRNA targeting highly probable single-stranded regions. Finally, the optimal properties of the siRNA were ensured through selection of those targeting 100% conserved, biologically functional short motifs. Validation of a predicted active (sh114) and a predicted inactive (sh113) (that was filtered out in Stage 8) silencer of the NS1 gene showed significant inhibition of the NS1 gene for sh114, with negligible decrease for sh113 which failed target accessibility. This demonstrated the fertility of this methodology.Contact: mahef@aucegypt.eduSupplementary Information: Supplementary data are available at Bioinformatics online. [ABSTRACT FROM PUBLISHER]

Genetic vaccines are safe cost-effective approaches to immunization but DNA immunization is an inefficient process. There is, therefore, a pressing need for adjuvants capable of enhancing the immunogenicity and effectiveness of these vaccines. This is particularly important for diseases for which successful vaccines are still lacking, such as cancer and infectious diseases including HIV-1/AIDS. Here we report an approach to enhance the immunogenicity of DNA vaccines involving the use of transcription factors of the Interferon regulatory factor (IRF) family, specifically IRF-1, IRF-3, and IRF-7 using the tat gene as model antigen. Balb/c mice were immunized by three intramuscular inoculations, using a DNA prime-protein boost protocol, with a DNA encoding tat of HIV-1 and the indicated IRFs and immune responses were compared to those induced by vaccination with tat DNA alone. In vivo administration of plasmid DNA encoding IRF-1, or a mutated version of IRF-1 deleted of the DNA-binding domain, enhanced Tat-specific immune responses and shifted them towards a predominant T helper 1-type immune response with increased IFN-γ production and cytotoxic T lymphocytes responses. Conversely, the use of IRF-3 or IRF-7 did not affect the tat-induced responses. These findings define IRF-1 and its mutated form as efficacious T helper 1-inducing adjuvants in the context of tat-based vaccination and also providing a new promising candidate for genetic vaccine development. J. Cell. Physiol. 224: 702–709, 2010. © 2010 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

The interferon regulatory factor 7 (IRF-7), a member of the IRF family of transcription factors, is a key player in the innate immune response against viral infections. Constitutive expression of IRF-7 is limited to peripheral blood lymphocytes and dendritic cells while in most cell types its expression can be induced by type I interferon (INF). IRF-7 is sequestered in the cytoplasm of uninfected cells and following viral infection, double-stranded RNA (dsRNA), or toll-like receptor (TLR) signaling, it becomes phosphorylated by TBK and IKK-i kinases. Phosphorylated IRF-7 migrates in the nucleus where it can activate IFN type I genes and other interferon-stimulated genes (ISGs). Here we report that the overexpression of a constitutively active form of IRF-7 binds and positively regulates the transcriptional activity of the promotor of IRF-1 and low molecular mass polypeptide-2 (LMP-2), two proteins that play a key role in adaptive immunity. The so far unrecognized role of IRF-7 in LMP-2 stimulation points to IRF-7 as a transcriptional regulator that bridges innate and adaptive immunity. [ABSTRACT FROM AUTHOR]

Interferon (IFN) regulatory factors (IRFs) constitute a family of transcriptional activators and repressors involved in the regulation of immune system, host defense, and cell growth. All members share conserved DNAbinding domains that recognize DNA sequences termed IRF-binding elements/ IFN-stimulated response elements (IRF-E/ISRE) present on the promoter of IFN-α/β and IFN-stimulated genes. An ISRE has been identified downstream of the transcription start site of the long terminal repeat (LTR) of human immunodeficiency virus-1 (HIV-1). Our previous results showed that among the IRF factors, IRF-1 is able to stimulate HIV-1 LTR transcription and its expression is induced by HIV-1, early, upon infection and before the expression of Tat. In this study we investigated the signal transduction pathway leading to HIV- 1-induced IRF-1 expression. Key IRF-1 promoter elements that mediate the activation of transcription upon induction by inflammatory cytokines are IFN-γ-activated sequences that bind members of the signal transducer and activator of transcription (STAT) family and binding sites for nuclear factor κB (NF-κB). Both STAT-1 and NF-κB activation were examined to determine putative molecular targets whose inhibition resulted in the inhibition of HIV-1 replication. The results show that at early time points after HIV-1 infection, NF-κB but not STAT-1 is activated. Moreover, a significant decrease in HIV-1 replication was observed upon de novo infection of Jurkat T cells expressing an NF-κB superrepressor (IκB-α2NΔ 4). These results suggest that in early phases of HIV-1 infection, before detectable cytokine production, NF-κB seems responsible for HIV-1-induced IRF-1 expression. [ABSTRACT FROM AUTHOR]

Interferons (IFNs) are pleiotropic cytokines that possess several biological activities and play a central role in basic and applied research as mediators of antiviral and antigrowth responses, modulators of the immune system, and therapeutic agents against viral diseases and cancer. Interferon regulatory factors (IRFs) have been identified together with signal transducers and activators of transcription (STAT) from studies on the type I IFN as well as IFN-stimulated (ISG) gene regulation and signaling. IRFs constitute a family of transcriptional activators and repressors implicated in multiple biological processes including regulation of immune responses and host defence, cytokine signaling, cell growth regulation, and hematopoietic development. All members share a well-conserved DNA binding domain at the NH2-terminal region that recognizes similar DNA sequences, termed IRF element (IRF-E)/interferon-stimulated response element (ISRE), present on the promoter of target genes. Recently, a sequence homologous to the ISRE has been identified downstream from the 5' human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR). This sequence is a binding site for IRF-1 and IRF-2. Here we briefly summarize the role of IRFs in the regulation of HIV-1 LTR transcriptional activity and virus replication. The overall effect of IRFs on HIV-1 replication will also be discussed in the context of strategies carried out by the virus to counteract the IFN-mediated host defences both in active replication and during the establishment of viral latency. [ABSTRACT FROM AUTHOR]

Background Chikungunya virus is an emerging mosquito-borne pathogen with a wide global distribution. With the severe morbidity that it causes, chikungunya virus is a major public health problem in the affected areas and poses a considerable risk for unaffected areas hosting competent vector populations. In the summer of 2017, Italy experienced a chikungunya virus outbreak that spread in the Lazio region and caused a secondary outbreak in the Calabrian village of Guardavalle, with a final case number of 436. The causative strain was recognized as an Indian Ocean lineage (IOL) virus. Methods To understand the underlying genetic and molecular features of the outbreak virus, viruses from mosquito pools and clinical samples were isolated in cell culture and subjected to whole-genome sequencing and genetic analyses. Results All 8 characterized genomes shared a high sequence identity. A distinct substitution pattern in the Italian 2017 viruses (including mutations in E1, E2, and nsP4) was partly shared with the Pakistani 2016 outbreak viruses. Evolutionary analyses indicate that these 2 recent outbreaks and several geographically widely distributed, travel-associated viruses form a cluster of rapidly emerging Indian-origin IOL viruses. Conclusions Our analyses show that the 2017 Italian outbreak virus belongs to a cluster of novel IOL chikungunya viruses originating in India. Their emergence calls for enhanced monitoring and strengthened preparedness measures, including vector control programs and raised awareness among general practitioners in countries potentially at risk. [ABSTRACT FROM AUTHOR]