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For cancer therapy and vaccination an amplified expression of the therapeutic gene is desired. Previously, we have developed a single-cycle adenovirus vector (SC-AdV) by deleting the adenovirus protease (PS) gene. In order to keep the E1 region intact within the PS-deleted adenoviruses, we examined the insertion of two transgenes under the control of a constitutive or inducible promoters. These were inserted between E4 and the right inverted terminal repeat in a wide variety of backbones with various combinations of PS, E3 and E4 deletion. Our data showed that PS-deleted adenoviruses, expressed transgenes as strongly as replication-competent AdVs in HEK293A and a variant of HeLa cells. In a head-to-head comparison in four human cell lines, we demonstrated that SC-AdV, was comparable for transgene expression efficacy with its replication-competent counterpart. However, the SC-AdV expresses its transgene 10 to 16,000 times higher than its replication-defective counterpart. • Transgenes should be inserted in the E4 region of single-cycle adenovirus (SC-AdV). • Equal transgene expression level between SC-AdV and replicative adenovirus. • Higher expression level in E4 deleted backbones. • SC-AdV expresses transgene significantly better than replication-defective. [ABSTRACT FROM AUTHOR]

Porcine epidemic diarrhea virus (PEDV) is a porcine enteropathogenic coronavirus causing severe watery diarrhea, vomiting, dehydration, and death in piglets. However, most commercial vaccines are developed based on the GI genotype strains, and have poor immune protection against the currently dominant GII genotype strains. Therefore, four novel replication-deficient human adenovirus 5-vectored vaccines expressing codon-optimized forms of the GIIa and GIIb strain spike and S1 glycoproteins were constructed, and their immunogenicity was evaluated in mice by intramuscular (IM) injection. All the recombinant adenoviruses generated robust immune responses, and the immunogenicity of recombinant adenoviruses against the GIIa strain was stronger than that of recombinant adenoviruses against the GIIb strain. Moreover, Ad-XT-tPA-Sopt-vaccinated mice elicited optimal immune effects. In contrast, mice immunized with Ad-XT-tPA-Sopt by oral gavage did not induce strong immune responses. Overall, IM administration of Ad-XT-tPA-Sopt is a promising strategy against PEDV, and this study provides useful information for developing viral vector-based vaccines. • Four Ad5-vectored vaccines expressing codon-optimized S and S1 proteins of the GIIa and GIIb PEDV strain were constructed. • All recombinant adenoviruses generated robust immune responses in mice. • Ad-XT-tPA-Sopt elicited optimal immune effects. • The neutralizing antibodies showed no significant differences between Ad-XT-tPA-Sopt and inactivated vaccine. • Ad-XT-tPA-Sopt is a promising vaccine against PEDV. [ABSTRACT FROM AUTHOR]

Human adenovirus type 7 (HAdV7) is commonly associated with febrile acute respiratory disease (ARD) outbreaks. We have reported that 10G12, a mouse monoclonal antibody (mAb) specifically recognizing and neutralizing HAdV7, is a promising candidate for humanization. In this study, we engineered the six variants of 10G12 with increased degree of humanization and investigated their biological activity. The humanized monoclonal antibody (mAb) 10G12-M2 was shown to retain the parental antibody's high binding affinity, specificity and potent efficacy of viral suppression. The mAb 10G12-M2 recognized a conformational neutralization epitope of the hexon protein. Complex structure-based molecular docking simulation showed that the hexon protein formed several interactions with 10G12-M2, including hydrogen bonds and salt bridges interaction. Physicochemical properties analysis of 10G12-M2 demonstrated that it is stable and desirable lead candidate. In general, 10G12-M2 had excellent biological activity after humanization combined with the potential for use in prophylactic or therapeutic applications against HAdV7. • The first report of the assess of the humanized mAb that can neutralize HAdV7. • A novel candidate therapeutic antibody with high binding affinity, specificity and potent efficacy of viral suppression. • A novel anti-HAdV7 antibody recognized a conformational neutralization epitope of the hexon protein. • A antibody had excellent physicochemical properties for use in prophylactic or therapeutic applications against HAdV7. [ABSTRACT FROM AUTHOR]

Epidemic keratoconjunctivitis (EKC) is a hazardous and highly contagious disease, with the potential to cause epidemic outbreaks in hospitals and other community settings. There are currently no approved drugs for human adenovirus (HAdV), the causative agent of EKC. To establish a novel drug screening system for ocular HAdV infections, we employed CRL11516, a non-cancerous but immortalized human corneal epithelial cell line. Brincidoforvir and 3′-deoxy-3′-fluorothymidine inhibit replication of HAdV species C type 1 (C1), C2, E4, and C6 to the same extent. This alternative assay system may allow for the evaluation of anti-HAdV activity and cell cytotoxicity of compounds within 2 days and without the need of the rabbit eye infection model. • A human epithelial cell line, CRL-11516, support infection of human adenoviruses. • Potency of anti-adenoviral agents can be evaluated within 2 days. • The assay system is a useful model of adenoviral keratoconjunctivitis in vitro. [ABSTRACT FROM AUTHOR]

Wild birds harbour a vast diversity of adenoviruses that remain uncharacterised with respect to their genome organisation and evolutionary relatedness within complex host ecosystems. Here, we characterise a novel adenovirus type within Aviadenovirus genus associated with severe necrotising hepatitis in a captive Timneh grey parrot, tentatively named as Timneh grey parrot adenovirus 1 (TpAdV-1). The TpAdV-1 genome is 39,867 bp and encodes 46 putative genes with seven hitherto not described ones. Comparative genomics and phylogenetic analyses revealed highest nucleotide identity with psittacine adenovirus 1 and psittacine adenovirus 4 that formed a discrete monophyletic clade within Aviadenovirus lineage suggesting a deep host co-divergent lineage within Psittaciformes hosts. Several recombination breakpoints were identified within the TpAdV-1 genome, which highlighted an ancient evolutionary relationship across the genera Aviadenovirus , Mastadenovirus and Atadenovirus. This study hints towards a host-adapted sub-lineage of avian adenovirus capable of having significant host virulence in Psittaciformes birds augmented with ecological opportunity. • A novel pathogenic Timneh grey parrot adenovirus 1 represents a distinct lineage involving a domestic–wildlife interface. • A novel genome might improve the accuracy of the phylogeny followed by a more complete taxonomy. • Possible host switch results in several recombination events which have contributed significantly to the evolution of adenoviruses. [ABSTRACT FROM AUTHOR]

In the adenovirus-infected cells, virus mRNAs are selectively exported to the cytoplasm by virus early gene products to facilitate virus replication. We previously showed AU-rich elements (AREs) containing mRNAs are exported to the cytoplasm and stabilized in infected cells. Here, we analyzed ribonucleoprotein (RNP) granules in the cytoplasm that are involved in mRNA degradation to elucidate the mechanism of ARE-mRNA stabilization in adenovirus infected cells. Our findings showed that processing bodies (PBs) aggregate, then almost all PBs are translocated to aggresomes formed by adenoviral gene products during the late phase of infection. Furthermore, E4orf3 was required for the PBs translocation, and the same domains of E4orf3-mutants required to change the form of promyelocytic leukemia bodies were also needed for PBs translocation. Luciferase activity showed that these domains were critical for miRNA- and ARE-mediated mRNA decay. These findings suggest that adenovirus changes the behavior of PBs to prevent ARE-mRNA downregulation. • PBs aggregated and translocated into the aggresomes during the late phase of adenovirus infected cells. • E4orf3 was required for the PBs translocation. • The PBs translocation inhibited ARE-mediated mRNA decay. [ABSTRACT FROM AUTHOR]

This research focuses on analyzing the dynamics of neutralizing antibody (nAbs) titers against type 5 adenovirus (Ad5) in the adult population of Russia following vaccination against the novel coronavirus infection with recombinant adenovirus type-5 COVID-19 vaccine (CanSino Biologics, China). The impact of the Ad5 vector on nAb titers was investigated using 302 blood serum samples from individuals who received a single dose of the Ad5-nCoV vector vaccine. The research revealed that 33.8% of adults in Russia had pre-existing anti-Ad5 nAbs before the pandemic. Notably, 40% of vaccinated individuals did not exhibit an increase in nAbs titers upon receiving the Ad5-based vaccine. However, in the group with no or low titers of anti-Ad5 nAbs (1:10–1:40), a significant 8-16-fold increase in nAb titers to Ad5 was observed. • The research revealed that 33.8% of adults in Russia had pre-existing anti-Ad5 nAbs before the pandemic. • 40% of vaccinated individuals did not exhibit an increase in nAbs titers upon receiving the Ad5-based vaccine. • A significant 8-16-fold increase in nAb titers to Ad5 was observed in the group with no or low titers of anti-Ad5 nAbs. [ABSTRACT FROM AUTHOR]

Adenovirus (Ad) early region 4 (E4) mutants activate cellular DNA damage responses (DDRs) that include non-homologous end joining (NHEJ) pathways mediated by the DNA repair kinase DNA-PK and its associated factors Ku70/Ku86. NHEJ results in concatenation of the viral linear double-stranded DNA genome and inhibits a productive infection. E4 proteins normally prevent activation of cellular DDRs in wild-type Ad type 5 (Ad5) infections, thereby promoting efficient viral growth. The purpose of this study was to evaluate the factors that govern DNA-PK activation during adenovirus infection. Our data indicate that viral DNA replication promotes DNA-PK activation, which is required for genome concatenation by NHEJ. Although the Mre11/Rad50/Nbs1 (MRN) DDR sensor complex is not required for DNA-PK activation, Mre11 is important for recruitment of the NHEJ factor Ku86 to viral replication centers. Our study addresses the interplay between the DNA-PK and MRN complexes during viral genome concatenation by NHEJ. • Viral DNA replication promotes DNA-PK activation and genome concatenation during E4-infection. • The MRN complex is not essential for DNA-PK autophosphorylation at Ser2056. • Ku86 is transiently localized to viral replication centers, which is promoted by the MRN complex. [ABSTRACT FROM AUTHOR]

Adenovirus (Ad) type 5 (Ad5) early region 4 (E4) proteins inhibit the DNA damage response (DDR) including activation of the DDR kinase ATM and its substrates, which can induce G2/M cell cycle arrest. Infection with Ad5 or the E4 deletion mutant H5 dl 1007 (1007) resulted in the accumulation of post G1 cells with > 2 N cellular DNA content. A greater fraction of cells with 4 N DNA content was observed in 1007 infections compared to Ad5; this population was dependent on activation of ATM. G2/M checkpoint kinases, phosphorylated Chk2 (pChk2), and phosphorylated Cdk1 (pCdk1) were upregulated in 1007 infections, and 1007 showed reduced levels of the mitosis marker phosphorylated (Ser10) histone 3 compared to Ad5. Our results show that E4 mutant activation of ATM induces G2/M arrest via activation of checkpoint kinases, thereby contributing to viral-mediated regulation of the cell cycle. • Ad infection induces cellular DNA replication while preventing cell division. • E4 mutant activation of ATM and downstream G2/M checkpoint kinases results in the accumulation of infected cells in G2/M. • E4 mutant infection prevents expression of the mitosis marker phosphorylated (Ser10) histone 3. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has paralyzed the global economy and resulted in millions of deaths globally. People with co-morbidities like obesity, diabetes and hypertension are at an increased risk for severe COVID-19 illness. This is of overwhelming concern because 42% of Americans are obese, 30% are pre-diabetic and 9.4% have clinical diabetes. Here, we investigated the effect of obesity on disease severity following SARS-CoV-2 infection using a well-established mouse model of diet-induced obesity. Diet-induced obese and lean control C57BL/6 N mice, transduced for ACE2 expression using replication-defective adenovirus, were infected with SARS-CoV-2, and monitored for lung pathology, viral titers, and cytokine expression. No significant differences in tissue pathology or viral replication was observed between AdV transduced lean and obese groups, infected with SARS-CoV-2, but certain cytokines were expressed more significantly in infected obese mice compared to the lean ones. Notably, significant weight loss was observed in obese mice treated with the adenovirus vector, independent of SARS-CoV-2 infection, suggesting an obesity-dependent morbidity induced by the vector. These data indicate that the adenovirus-transduced mouse model of SARS-CoV-2 infection, as described here and elsewhere, may be inappropriate for nutrition studies. • Lean and obese C57BL/6 N mice transduced with a replication-defective adenovirus encoding human ACE2 became susceptible to SARS-CoV-2 infection. • High levels of infectious virus and viral RNA were detected in the lungs of infected lean and obese mice. • Inoculation with the adenovirus vector at this dose caused an obesity-specific morbidity in C57BL/6 N mice. [ABSTRACT FROM AUTHOR]

Efficacy of oncolytic, conditionally-replicating adenovirus (CRAd) vectors can be enhanced by "arming" the vector with therapeutic transgenes. We examined whether inclusion of an intact early region 3 (E3) and the reptilian reovirus fusogenic p14 fusion-associated small transmembrane (FAST) protein enhanced vector efficacy. The p14 FAST transgene was cloned between the fiber gene and E4 region, with an upstream splice acceptor for replication-dependent expression from the major late promoter. In A549 cells, this vector expressed p14 FAST protein at very low levels, and showed a poor ability to mediate cell-cell fusion, relative to a similar vector encoding p14 FAST within the E3 deletion. Although expression of E3 proteins from the CRAd increased plaque size, poor expression of p14 FAST protein compromised the fusogenic capacity of the vector. Thus, location of a therapeutic transgene within a CRAd can significantly impact expression of the transgene and is an important consideration in vector design. • HAdV-5 early region 3 proteins and p14 FAST protein can synergize to promote cancer cell killing. • Transgenes cloned between the HAdV-5 fiber gene and early region 4 are expressed at low level. • Transgenes cloned within the early region 3 deletion of HAd-5 vectors are expressed at high level. [ABSTRACT FROM AUTHOR]

We report the discovery and characterization of a novel adenovirus, Zoothera dauma adenovirus (ZdAdV), from a wild bird species, Zoothera dauma (Scaly thrush). This new atadenovirus was discovered by metagenomic sequencing without virus cultivation. Analyses of the full genome sequence revealed that this new virus is a distinct member of the genus Atadenovirus and represents a novel species. ZdAdV has a genome of 34,760 bp with 28 predicted genes and 39% GC content. ZdAdV is the first atadenovirus to contain ORF19, a gene previously found only in aviadenoviruses. Phylogenetic analysis of ORF19 suggests that it was acquired by ZdAdV through horizontal gene transfer from an aviadenovirus. By analyzing all orthologous genes of aviadenovirus, mastadenovirus, atadenovirus, and siadenovirus, we also found potential horizontal gene transfer for the E4 gene in Pigeon aviadenovirus B. Our study widens our knowledge concerning the genetic diversity and evolutionary history of atadenoviruses and their potential for cross-species transmission. • The article describes the discovery of a new adenovirus, Zoothera dauma adenovirus (ZdAdV), found in the Scaly thrush. • ZdAdV belongs to the Atadenovirus genus and is distinct from other members within this group. • The genome of ZdAdV measures 34,760 bp and contains 28 predicted genes, distinguishing it from other known adenoviruses. • ZdAdV is the first atadenovirus to harbor ORF19, a gene previously observed exclusively in aviadenoviruses. • Phylogenetic analyis of ORF19 and E4 genes show evidence for horizontal gene transfer within diferent adenovirus species. [ABSTRACT FROM AUTHOR]

Human adenovirus (HAdV) can cause severe disease in certain at-risk populations such as newborns, young children, the elderly and individuals with a compromised immune system. Unfortunately, no FDA-approved antiviraldrug is currently available for the treatment of HAdV infections. Within the nucleus of infected cells, the HAdV genome associates with histones and forms a chromatin-like structure during early infection, and viral gene expression appears to be regulated by cellular epigenetic processes. Thus, one potential therapeutic strategy to combat HAdV disease may be to target the cellular proteins involved in modifying the viral nucleoprotein structure and facilitating HAdV gene expression and replication. We have screened a panel of small molecules that modulate the activity of epigenetic regulatory proteins for compounds affecting HAdV gene expression. Several of the compounds, specifically chaetocin, gemcitabine and lestaurtinib, reduced HAdV recovery by 100- to 1000-fold, while showing limited effects on cell health, suggesting that these compounds may indeed be promising as anti-HAdV therapeutics. [ABSTRACT FROM AUTHOR]

CD8 T cells contribute to effective clearance of mouse adenovirus type 1 (MAV-1) and to virus-induced pulmonary inflammation. We characterized effects of a CD8 T cell effector, TNF, on MAV-1 pathogenesis. TNF inhibited MAV-1 replication in vitro. TNF deficiency or immunoneutralization had no effect on lung viral loads or viral gene expression in mice infected intranasally with MAV-1. Absence of TNF delayed virus-induced weight loss and reduced histological evidence of pulmonary inflammation, although concentrations of proinflammatory cytokines and chemokines in bronchoalveolar lavage fluid (BALF) were not significantly affected. BALF concentrations of IL-10 were greater in TNF-deficient mice compared to controls. Our data indicate that TNF is not essential for control of viral replication in vivo , but virus-induced TNF contributes to some aspects of immunopathology and disease. Redundant CD8 T cell effectors and other aspects of immune function are sufficient for antiviral and pro-inflammatory responses to acute MAV-1 respiratory infection. • TNF inhibits MAV-1 replication in vitro. • TNF deficiency does not impair control of MAV-1 replication in the lungs. • TNF deficiency delays virus-induced weight loss. • TNF reduces histological evidence of pulmonary inflammation. • TNF deficiency does not affect proinflammatory cytokine production in airways. [ABSTRACT FROM AUTHOR]

Human adenovirus serotype 7 (HAdV-7), belonging to species B, has caused severe lower respiratory tract diseases and even deaths recently. However, no adenovirus vaccine or therapeutic is available thus far. In this study, a HAdV-7-specific human monoclonal antibody (HMAb), 3-3E, isolated from single plasma cells obtained from the peripheral blood mononuclear cells of HAdV-7-infected patients showed potent HAdV-7 neutralization activity. The results showed HMAb 3-3E only binds to the hexon protein of intact HAdV-7 or the recombinant hexon protein and it does not bind to other intact virion particles. This could mean the antibody recognizes a conformational epitope of the hexon protein. Further, HMAb 3-3E potently neutralized HAdV-7 in vitro at low concentrations. In vivo studies showed HMAb 3-3E protected from HAdV-7 infection in a murine model. Therefore, HMAb 3-3E is promising as a safe and effective prophylactic and therapeutic treatment for HAdV-7 infection. [ABSTRACT FROM AUTHOR]

Human adenovirus (HAdV) can cause severe disease and death in both immunocompromised and immunocompetent patients. The current standards of treatment are often ineffective, and no approved antiviral therapy against HAdV exists. We report here the design and validation of a fluorescence-based high-content screening platform for the identification of novel anti-HAdV compounds. The screen was conducted using a wildtype-like virus containing the red fluorescent protein (RFP) gene under the regulation of the HAdV major late promoter. Thus, RFP expression allows monitoring of viral late gene expression (a surrogate marker for virus replication), and compounds affecting virus growth can be easily discovered by quantifying RFP intensity. We used our platform to screen ~1200 FDA-approved small molecules, and identified several cardiotonic steroids, corticosteroids and chemotherapeutic agents as anti-HAdV compounds. Our screening platform provides the stringency necessary to detect compounds with varying degrees of antiviral activity, and facilitates drug discovery/repurposing to combat HAdV infections. [ABSTRACT FROM AUTHOR]

Species Human mastadenovirus E (HAdV-E) comprises several simian types and a single human type: HAdV-E4, a respiratory and ocular pathogen. RFLP analysis for the characterization of intratypic genetic variability has previously distinguished two HAdV-E4 clusters: prototype (p)-like and a-like. Our analysis of whole genome sequences confirmed two distinct lineages, which we refer to as phylogroups (PGs). PGs I and II comprise the p- and a-like genomes, respectively, and differ significantly in their G + C content (57.7% ± 0.013 vs 56.3% ± 0.015). Sequence differences distinguishing the two clades map to several regions of the genome including E3 and ITR. Bayesian analyses showed that the two phylogroups diverged approximately 602 years before the present. A relatively faster evolutionary rate was identified for PG II. Our data provide a rationale for the incorporation of phylogroup identity to HAdV-E4 strain designation to reflect the identified unique genetic characteristics that distinguish PGs I and II. • Two major phylogroups are identifiable among HAdV-E4 strains circulating since 1953. • Phylogroups I and II differ in their G + C content and evolutionary rates. • Phylogroup-specific mutations map to multiple coding regions of the genome. • The two phylogroups diverged approximately 600 years before the present. • Time to the most recent common ancestor in each phylogroup dates to <100 years. [ABSTRACT FROM AUTHOR]

Rabies continues to poses serious threats to the public health in many countries. The development of novel inexpensive, safe and effective vaccines has become a high priority for rabies control worldwide. We previously generated a novel recombinant rabies vaccine by cloning rabies virus glycoprotein into a chimpanzee adenoviral vector, termed ChAd68-Gp. The present study evaluated the immune responses and protection afforded by this vaccine in beagle dogs. The results demonstrated that intramuscular immunization with both low-dose and high-dose of ChAd68-Gp induced strong immune responses and provided complete protection in beagles even at low-dose. However, when administered orally, high-dose vaccination was protective while low-dose vaccination was ineffective. Further investigation indicated that the low-pH value of gastric juice in the stomach of beagles might decompose the adenovirus. Therefore, suitable formulation for adenovirus-based oral vaccine should be considered and developed. The chimpanzee adenovirus-vectored rabies vaccine ChAd68-Gp warrants extensive test for clinical application. [ABSTRACT FROM AUTHOR]

The large GTPase dynamin 2 controls both endosomal fission and microtubule acetylation. Here we report that dynamin 2 alters microtubules and regulates the trafficking of human adenovirus type 37. Dynamin 2 knockdown by siRNA in infected cells resulted in accumulation of acetylated tubulin, repositioning of microtubule organizing centers (MTOCs) closer to cell nuclei, increased virus in the cytosol (with a compensatory decrease in endosomal virus), reduced proinflammatory cytokine induction, and increased binding of virus to the nucleoporin, Nup358. These events led to increased viral DNA nuclear entry and viral replication. Overexpression of dynamin 2 generated opposite effects. Therefore, dynamin 2 inhibits adenovirus replication and promotes innate immune responses by the infected cell. MTOC transposition in dynamin 2 knockdown promotes a closer association with nuclear pore complexes to facilitate viral DNA delivery. Dynamin 2 plays a key role in adenoviral trafficking and influences host responses to infection. [ABSTRACT FROM AUTHOR]

Abstract Adenovirus (Ad) type 5 (Ad5) E4 deletion mutants including H5 dl 1007 (E4-) induce a DNA damage response (DDR) that activates the kinase ataxia-telangiectasia mutated (ATM), which can interfere with efficient viral DNA replication. We find that localization of active phosphorylated ATM (pATM) to E4- viral replication centers (VRCs) is important for its inhibitory effect. ATM is necessary for localization of RNF8 and 53BP1 to E4 mutant VRCs, while recruitment of DDR factors Mre11, Mdc1 and γH2AX is ATM-independent, raising the possibility that ATM may affect viral chromatin at VRCs. We assessed E4- and Ad5 chromatin organization by micrococcal nuclease (MN) digestion. A significant fraction of Ad5 DNA is somewhat resistant to MN digestion, whereas E4- DNA is more susceptible. ATM inhibition increases the fraction of E4- DNA that is resistant to MN digestion. Our results address possible mechanisms through which ATM inhibits E4- DNA replication. [ABSTRACT FROM AUTHOR]

Abstract As a novel duck adenovirus 3 (DAdV-3) infection caused significant economic losses to the poultry industry in China, there is an urgent need to develop a safe and effective vaccine. In the research, fiber-1 and fiber-2 proteins were expressed and purified, respectively. To evaluate the immunogenicity of the two recombinant proteins, we investigated the IgY antibodies and virus-neutralizing antibodies in duck sera. The protective efficacy was evaluated by mortality, virus shedding and histopathological examinations after challenged with the DAdV-3. Results showed that the IgY antibody levels of the fiber-2 group was significantly higher than that of the fiber-1 group and inactivated vaccine group. Ducks vaccinated with fiber-2 group provided full protection with no mortality, no virus shedding and no histological lesions, superior to other groups. These results suggest that the fiber-2 protein can be an ideal candidate for subunit vaccine against the disease. Highlights • The fiber-2 protein increased levels of humoral antibody, and provided full protection against the novel duck adenovirus 3. [ABSTRACT FROM AUTHOR]

Abstract E1A is the main transforming protein in mastadenoviruses. This work uses bioinformatics to extrapolate experimental knowledge from Human adenovirus serotype 5 and 12 E1A proteins to all known serotypes. A conserved domain architecture with a high degree of intrinsic disorder acts as a scaffold for multiple linear motifs with variable occurrence mediating the interaction with over fifty host proteins. While linear motifs contribute strongly to sequence conservation within intrinsically disordered E1A regions, motif repertoires can deviate significantly from those found in prototypical serotypes. Close to one hundred predicted residue-residue contacts suggest the presence of stable structure in the CR3 domain and of specific conformational ensembles involving both short- and long-range intramolecular interactions. Our computational results suggest that E1A sequence conservation and co-evolution reflect the evolutionary pressure to maintain a mainly disordered, yet non-random conformation harboring a high number of binding motifs that mediate viral hijacking of the cell machinery. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM) is a devastating malignant brain tumor. Current therapeutic strategies targeting tumor cells have limited efficacy owing to the immunosuppressive microenvironment. Previous work demonstrated that the targeted Ad5-Ki67/IL-15 could specifically kill tumor cells and decrease the angiogenic capacity in vitro. However, the efficacy of this virus in vivo and its effect on the tumor microenvironment (TME) has not been elucidated. In this study, we found that the Ad5-Ki67/IL-15 treatment down-regulated PD-L1 expression of glioma cells. More importantly, Ad5-Ki67/IL-15 also remodeled the tumor microenvironment via increasing intratumoral T cell infiltration and PD-L1 improvement in a GBM model, as well as the increase of antitumor cytokines, thereby improving the efficacy of GBM treatment. Furthermore, a combination of Ad5-Ki67/IL-15 with PD-L1 blockade significantly inhibits tumor growth in the GBM model. These results provide new insight into the therapeutic effects of targeted oncolytic Ad5-Ki67/IL-15 in patients with GBM, indicating potential clinical applications. • Ad5-Ki67/IL-15 promotes intratumoral T cell infiltration and PD-L1 improvement in glioma model. • Combination of Ad5-Ki67/IL-15 with PD-L1 blockade generates potent antitumor efficacy. • Ad5-Ki67/IL-15 treatment is a promising approach for GBM patients in future. [ABSTRACT FROM AUTHOR]

The L6 region of bovine adenovirus-3 (BAdV-3) encodes unspliced and spliced proteins named 22K and 33K, respectively. Earlier, anti-22K sera detected two proteins of 42- and 37-kDa in infected cells and 42-kDa protein in transfected cells. Here, we demonstrate that 22K protein localizes to the nucleus of BAdV-3 infected or transfected cells. Analysis of mutant 22K proteins suggested that amino acids 231–250 of non-conserved C-terminus of 22K are required for nuclear localization. The nuclear import of 22K appears to utilize multiple importin (α-5 and α-7) of importin α/β nuclear import pathway. Mutational analysis of 22K identified four basic residues 238 RRRK 241 , which apparently are essential for the nuclear localization of 22K. Our results suggest that the nuclear localization of 22K appear essential for virus replication and production of progeny BAdV-3. Furthermore, we demonstrate that N-terminus amino acid 35–65 conserved in 22K and 33K interact with 52K protein in BAdV-3 infected cells. [ABSTRACT FROM AUTHOR]

CD8 T cells play a key role in clearance of mouse adenovirus type 1 (MAV-1) from the lung and contribute to virus-induced airway inflammation. We tested the hypothesis that interactions between Fas ligand (FasL) and Fas mediate the antiviral and proinflammatory effects of CD8 T cells. FasL and Fas expression were increased in the lungs of C57BL/6 (B6) mice during MAV-1 respiratory infection. Viral replication and weight loss were similar in B6 and Fas-deficient ( lpr ) mice. Histological evidence of pulmonary inflammation was similar in B6 and lpr mice, but lung mRNA levels and airway proinflammatory cytokine concentrations were lower in MAV-1-infected lpr mice compared to infected B6 mice. Virus-induced apoptosis in lungs was not affected by Fas deficiency. Our results suggest that the proinflammatory effects of CD8 T cells during MAV-1 infection are mediated in part by Fas activation and are distinct from CD8 T cell antiviral functions. [ABSTRACT FROM AUTHOR]

The exterior minor protein IX of adenoviruses (AdVs) is a frequent target of attachment of antigens and the modified AdVs are being used as potent vaccine platforms. The organization of protein IX is disticntly different between human adenoviruses (HAdVs) and non-HAdVs. The analysis of solvent accessibility, based on the near atomic resolution structures, suggests that the C-terminal residues of IX are more accessible in non-HAdVs (e.g., bovine adenovirus) than in HAdVs. Although the C-terminal fusions of IX are displayed on the capsid surface, they could disrupt the formation of tetrameric coiled-coils (4-HLXB) in HAdVs due to steric hinderance, thereby potentially affecting the capsid stability. Importantly, the parallel-antiparallel arrangement of helices seen in the 4-HLXB is not condusive for IX C-terminal fusions in HAdVs. In contrast, the parallel trimeric C-terminal coiled-coils in non-HAdVs are unlikely to be affected by the attachment of antigens and more efficiently displayed on the AdV surface. [ABSTRACT FROM AUTHOR]

The clinical use of many adenovirus vaccine vectors (AdVs) is limited by the presence of pre-existing antibodies in human populations, which prevent common AdVs from transducing cells and expressing immunogenic gene products. Rare serotype AdVs, such as HAdV-28D can bypass pre-existing immunity. However, rare AdVs stimulate high-levels of type I interferon (IFN), which suppresses antigenic gene expression and therefore limits immunogenicity. Recent studies identified Gas6 as a factor that connects enveloped viruses to host-cell receptor tyrosine kinases, in turn generating signaling cascades that antagonize type I IFN responses. We discovered that Gas6 bound to the fiber proteins of common AdV serotypes, such as HAdV-5C, with a higher affinity than rare HAd-28D fibers. AdV-associated Gas6 suppressed IFN production by common AdVs and enhanced long-term expression of AdV encoded genes. We hypothesize that rare AdV serotypes might be engineered to include Gas6 binding motifs, thereby generating novel vectors that are more effective. [ABSTRACT FROM AUTHOR]

Recently, increasing attention has been focused on the influence of sex on the course of infectious diseases. Thus far, the best-documented examples point toward an immune-mediated mechanism: the generally stronger immune response in females can result in a faster clearance of the pathogen or, conversely, a more severe immune-mediated pathology. Here, we report that human species C adenoviruses replicate more and cause more pathology in male Syrian hamsters than in females. We also show that this sex disparity is not caused by a stronger immune response to the infection by the female hamsters. Rather, the liver of male hamsters is more susceptible to adenovirus infection: after intravenous injection, more hepatocytes become infected in male animals than in females. We hypothesize that Kupffer cells (hepatic tissue macrophages) of female animals are more active in sequestering circulating virions, and thus protect hepatocytes more efficiently than those of males. [ABSTRACT FROM AUTHOR]

We previously selected muscle binding peptides 12.51 and 12.52 from "context-specific" phage display libraries for introduction into adenovirus (Ad) vectors. In this work, these peptides were inserted into the hypervariable region (HVR) 5 loop of the Ad5 hexon protein to display 720 peptides per virions. HVR-12.51 and 12.52 increased transduction of C2C12 cells up to 20-fold when compared to unmodified Ad5. 12.51 increased in vivo muscle transduction 2 to 7-fold over unmodified Ad after intramuscular injection in mice and hamsters. 12.52 did not increase muscle transduction. Notably, insertion of 12.51 into the hexon reduced liver transduction 80-fold when compared to unmodified Ad5 after intravenous injection. Increased muscle transduction in mice translated into increased immune responses after gene-based vaccination. These data suggest there are merits to retargeting and detargeting benefits to modifying the hexons of Ads with peptide ligands. [ABSTRACT FROM AUTHOR]

Cellular transformation by adenovirus E1A requires targeting TRRAP, a scaffold protein which helps assemble histone acetyltransferase complexes, including the NuA4 complex. We recently reported that E1A and E1A 1–80 (N-terminal 80 aa) promote association of the proto-oncogene product MYC with the NuA4 complex. The E1A N-terminal TRRAP-targeting (ET) domain is required for E1A 1–80 to interact with the NuA4 complex. We demonstrate that an ET-MYC fusion associates with the NuA4 complex more efficiently than does MYC alone. Because MYC regulates genes for multiple cellular pathways, we performed global RNA-sequence analysis of cells expressing MYC or ET-MYC, and identified a panel of genes (262) preferentially activated by ET-MYC and significantly enriched in genes involved in gene expression and ribosome biogenesis, suggesting that E1A enhances MYC association with the NuA4 complex to activate a set of MYC target genes likely involved in cellular proliferation and cellular transformation by E1A and by MYC. [ABSTRACT FROM AUTHOR]

The proteome and phosphoproteome of non-structural proteins of Adenovirus type 2 (Ad2) were time resolved using a developed mass spectrometry approach. These proteins are expressed by the viral genome and important for the infection process, but not part of the virus particle. We unambiguously confirm the existence of 95% of the viral proteins predicted to be encoded by the viral genome. Most non-structural proteins peaked in expression at late time post infection. We identified 27 non-redundant sites of phosphorylation on seven different non-structural proteins. The most heavily phosphorylated protein was the DNA binding protein (DBP) with 15 different sites. The phosphorylation occupancy rate could be calculated and monitored with time post infection for 15 phosphorylated sites on various proteins. In the DBP, phosphorylations with time-dependent relation were observed. The findings show the complexity of the Ad2 non-structural proteins and opens up a discussion for potential new drug targets. [ABSTRACT FROM AUTHOR]

Fiber and penton base overproduced in adenovirus (Ad) infected cells can be secreted prior to progeny release and thereby regulate progeny spread. We aimed to investigate the mechanisms of fiber and penton base secretion in Ad2- or Ad5-infected A549 cells. Our flow cytometry analyses detected abundant surface fiber molecules, but little penton base molecules at 12 h post infection. Immunogold staining combined with transmission electron microscopic analyses revealed separate, non-co-localized release of fiber and penton base in the proximity of the plasma membrane. Depolymerization of microtubule and actin cytoskeletons, and inhibition of Rock kinase and myosin II activity together demonstrated cytoskeletal network-dependent fiber secretion. Inhibition of intracellular calcium [Ca 2+ ] i signaling caused diminished fiber secretion, which was associated with diminished progeny production. Thus, fiber and penton base are actively and separately secreted during the early stages of Ad2 or Ad5 infection, their secretion may play important role in Ad life cycle. [ABSTRACT FROM AUTHOR]

The unique repertoire of genes that characterizes the early region 3 (E3) of the different species of human adenovirus (HAdV) likely contributes to their distinct pathogenic traits. The function of many E3 CR1 proteins remains unknown possibly due to unidentified intrinsic properties that make them difficult to express ectopically. This study shows that the species HAdV-B- and HAdV-E-specific E3 CR1 genes can be expressed from vectors carrying the HAdV tripartite leader (TPL) sequence but not from traditional mammalian expression vectors. Insertion of the TPL sequence upstream of the HAdV-B and HAdV-E E3 CR1 open reading frames was sufficient to rescue protein expression from pCI-neo constructs in transfected 293T cells. The detection of higher levels of HAdV-B and HAdV-E E3 CR1 transcripts suggests that the TPL sequence may enhance gene expression at both the transcriptional and translational levels. Our findings will facilitate the characterization of additional AdV E3 proteins. [ABSTRACT FROM AUTHOR]

Enadenotucirev (EnAd) is a group B oncolytic adenovirus developed for systemic delivery and currently undergoing clinical evaluation for advanced cancer therapy. For differentiated carcinomas, systemic delivery would likely expose virus particles to the basolateral surface of cancer cells rather than the apical surface encountered during natural infection. Here, we compare the ability of EnAd and adenovirus type-5 (Ad5) to infect polarised colorectal carcinoma cells from the apical or basolateral surfaces. Whereas Ad5 infection was more efficient via the apical than basolateral surface, EnAd readily infected cells from either surface. Progeny particles from EnAd were released preferentially via the apical surface for all cell lines and routes of infection. These data further support the utility of group B adenoviruses for systemic delivery and suggest that progeny virus are more likely to be released into the tumour rather than back through the basolateral surface into the blood stream. [ABSTRACT FROM AUTHOR]

Competing roles of coevolution, selective pressure and recombination are an emerging interest in virus evolution. We report a novel aviadenovirus from captive red-bellied parrots ( Poicephalus rufiventris ) that uncovers evidence of deep recombination among aviadenoviruses. The sequence identity of the virus was most closely related to Turkey adenovirus D (42% similarity) and other adenoviruses in chickens, turkeys and pigeons. Sequencing and comparative analysis showed that the genome comprised 40,930 nucleotides containing 42 predicted open reading frames (ORFs) 19 of which had strong similarity with genes from other adenovirus species. The new genome unveiled a lineage that likely participated in deep recombination events across the genus Aviadenovirus accounting for an ancient evolutionary relationship. We hypothesize frequent host switch events and recombination among adenovirus progenitors in Galloanserae hosts caused the radiation of extant aviadenoviruses and the newly assembled Poicephalus adenovirus genome points to a potentially broader host range of these viruses among birds. [ABSTRACT FROM AUTHOR]

A human adenovirus (Ad5) vectored foot-and-mouth disease virus (FMDV) O1-Manisa subunit vaccine (Ad5-O1Man) was engineered to deliver FMDV O1-Manisa capsid and capsid-processing proteins. Swine inoculated with Ad5-O1Man developed an FMDV-specific humoral response as compared to animals inoculated with an empty Ad5-vector. Vaccinated animals were completely protected against homologous challenge at 7 or 21 days post-vaccination. Potency studies exhibited a PD50 of about 10 7 pfu/animal while a dose of 4×10 7 pfu/animal fully protected swine against FMDV intradermal challenge. In-vitro cross-neutralization analysis distinctly predicted that swine vaccinated with Ad5-O1Man would be protected against challenge with homologous FMDV O1Man Middle East-South Asia (ME-SA) topotype and also against recent outbreak strains of Mya-98 South East Asia (SEA) lineage including O1-UK-2001 and O1-South Korea-2010. These results indicate that recombinant Ad5-O1Man is an effective, safe and cross-reacting vaccine that could potentially be used preventively and in outbreak situations, to control FMDV O Mya-98 lineage in swine. [ABSTRACT FROM AUTHOR]

The abundance and accessibility of a primary virus receptor are critical factors that impact the susceptibility of a host cell to virus infection. The Coxsackievirus and adenovirus receptor (CAR) has two transmembrane isoforms that occur due to alternative splicing and differ in localization and function in polarized epithelia. To determine the relevance of isoform-specific expression across cell types, the abundance and localization of both isoforms were determined in ten common cell lines, and correlated with susceptibility to adenovirus transduction relative to polarized primary human airway epithelia. Data show that the gene and protein expression for each isoform of CAR varies significantly between cell lines and polarization, as indicated by high transepithelial resistance, is inversely related to adenovirus transduction. In summary, the variability of polarity and isoform-specific expression among model cells are critical parameters that must be considered when evaluating the clinical relevance of potential adenovirus-mediated gene therapy and anti-adenovirus strategies. [ABSTRACT FROM AUTHOR]

In this study, we conducted the clinicopathological characterization of a non-pathogenic FAdV-D serotype 11 strain MX95, isolated from healthy chickens, and its entire genome was sequenced. Experiments in SPF chickens revealed that the strain is a non-pathogenic virus that did not cause death at challenge doses of 1×10 6 TCID50. Additionally, the infection in SPF chickens caused no apparent damage in most of the organs analyzed by necropsy and histopathology, but it did cause inclusion body hepatitis; nevertheless it did not generate severe infectious clinical symptoms. The virus was detected in several chicken organs, including the lymphoid organs, by real-time polymerase chain reaction (PCR) until 42 days. The genome of FAdV-11 MX95 has a size of 44,326 bp, and it encodes 36 open reading frames (ORFs). Comparative analysis of the genome indicated only 0.8% dissimilarity with a highly virulent serotype 11 that was previously reported. [ABSTRACT FROM AUTHOR]

Human adenovirus infects terminally differentiated cells and to replicate it must induce S-phase. The chief architects that drive adenovirus-infected cells into S-phase are the E1A proteins, with 5 different isoforms expressed during infection. E1A remodels the infected cell by associating with cellular factors and modulating their activity. The C-terminus of E1A is known to bind to only a handful of proteins. We have identified a novel E1A C-terminus binding protein, Ku70 (XRCC6), which was found to bind directly within the CR4 of E1A from human adenovirus type 5. Depletion of Ku70 reduced virus growth, possibly by activating the DNA damage response pathway. Ku70 was found to localize to viral replication centers and associate with the viral genome. Ku70 was also recruited to cellular cell cycle regulated promoters following viral infection. Our study has identified, for the first time, Ku70 as a novel E1A-binding protein which affects virus life cycle. [ABSTRACT FROM AUTHOR]

The adenovirus E1A 243R oncoprotein targets TRRAP, a scaffold protein that assembles histone acetyltransferase (HAT) complexes, such as the NuA4/Tip60 complex which mediates transcriptional activity of the proto-oncogene MYC and helps determine the cancer cell phenotype. How E1A transforms cells through TRRAP remains obscure. We performed proteomic analysis with the N-terminal transcriptional repression domain of E1A 243R (E1A 1-80) and showed that E1A 1-80 interacts with TRRAP, p400, and three other members of the NuA4 complex - DMAP1, RUVBL1 and RUVBL2 - not previously shown to associate with E1A 243R. E1A 1-80 interacts with these NuA4 components and MYC through the E1A TRRAP-targeting domain. E1A 243R association with the NuA4 complex was demonstrated by co-immunoprecipitation and analysis with DMAP1, Tip60, and MYC. Significantly, E1A 243R promotes association of MYC/MAX with the NuA4/Tip60 complex, implicating the importance of the MYC/NuA4 pathway in cellular transformation by both MYC and E1A. [ABSTRACT FROM AUTHOR]

Foot-and-mouth-disease (FMD) remains the most infectious livestock disease worldwide. Although commercially available inactivated or adenovirus-vectored-vaccines (Ad5-FMD) are effective, they require 5–7 days to induce protection. Therefore, new control strategies that stimulate rapid immune responses are needed. Expression of bovine interferon λ3 using the Ad5-vector platform (Ad5-boIFNλ3) is able to delay disease in cattle, but clinical signs appear at 9 days after challenge. We hypothesized that combination of Ad5-boIFNλ3 and Ad5-FMD could induce immediate and lasting protection against FMD. Cattle were vaccinated with an Ad5-FMD, Ad5-boIFNλ3, or the combination of both, followed by challenge at three days post-immunization. All animals treated with Ad5-FMD combined with Ad5-boIFNλ3 were fully protected against FMD, despite the absence of systemic neutralizing antibodies or antiviral activity at the time of challenge. Induction of a strong cell-mediated immune response suggested that Ad5-boIFNλ3 is able to act as an adjuvant of Ad5-FMD vaccine in cattle. [ABSTRACT FROM AUTHOR]

Deoxyuridine 5′-triphosphate pyrophosphatase (dUTPase), a ubiquitous enzyme that catalyzes the hydrolysis of dUTP to dUMP and found in many viruses, has yet to be identified in fowl adenovirus 9 (FAdV-9). By a multiple alignment of dUTPase amino acid sequences, FAdV-9 ORF1 contained the five conserved motifs that define the protein family, and encoded a functional dUTPase. Moreover, transcription and protein expression patterns were characterized, indicating that dUTPase was transcribed from 2 h post-infection (h.p.i.) and translated from 6 h.p.i., and both continued to the late phase of virus infection. An HA-tagged dUTPase recombinant virus was generated, and dUTPase was found to be localized in both the cytoplasm and nucleus in chicken hepatoma cells (CH-SAH). A dUTPase knockout virus was generated and compared with the wild-type virus, showing that dUTPase upregulated the expression of type I interferons, but was not required for viral DNA or virus replication in CH-SAH cells. [ABSTRACT FROM AUTHOR]

The use of continuous cell lines derived from the African green monkey kidney (AGMK) has led to major advances in virus vaccine development. However, to date, these cells have not been used to facilitate the creation of human adenoviruses because most human adenoviruses undergo abortive infections in them. Here, we report the susceptibility of AGMK-derived cells to adenovirus 11p (Ad11p) infection. First, we showed that CD46 molecules, which act as receptors for Ad11p, are expressed in AGMK cells. We then monitored Ad11p replication by measuring GFP expression as an indicator of viral transcription. We found that AGMK-derived cells were as capable as carcinoma cells at propagating full-length replication-competent Ad11p (RCAd11p) DNA. Of the AGMK cell lines tested, Vero cells had the greatest capacity for adenovirus production. Thus, AGMK cells can be used to evaluate RCAd11p-mediated gene delivery, and Vero cells can be used for the production of RCAd11pGFP vectors at relatively high yields. [ABSTRACT FROM AUTHOR]

This study aimed to characterize a novel adenovirus (AdV) isolated from diseased Muscovy ducks in China. After the AdV was successfully propagated in duck embryo fibroblasts, the morphological and physicochemical properties of the virions were studied by electron microscopy and different tests. The results of the analyses were in conformity with AdV properties. The full genome sequence was determined and analyzed. The new isolate (named CH-GD-12-2014) shared over 91% sequence identity with duck AdV-2 representing the species Duck aviadenovirus B. The most important distinguishing feature between the two DAdV strains was the presence of a second fiber gene in the Chinese isolate. Phylogeny reconstruction confirmed the affiliation of the virus with goose and duck AdVs in the genus Aviadenovirus . Experimental infection resulted in embryo death, and intramuscular inoculation provoked morbidity and mortality among ducks and chickens. [ABSTRACT FROM AUTHOR]

Oncolytic adenoviruses (OAds) are very promising for the treatment of lung cancer. However, OAd-based monotherapeutics have not been effective during clinical trials. Therefore, the effectiveness of virotherapy must be enhanced by combining OAds with other therapies. In this study, the therapeutic potential of OAd in combination with temozolomide (TMZ) was evaluated in lung cancer cells in vitro and in vivo . The combination of OAd and TMZ therapy synergistically enhanced cancer cell death; this enhanced cancer cell death may be explained via three related mechanisms: apoptosis, virus replication, and autophagy. Autophagy inhibition partially protected cancer cells from this combined therapy. This combination significantly suppressed the growth of subcutaneous H441 lung cancer xenograft tumors in athymic nude mice. In this study, we have provided an experimental rationale to test OAds in combination with TMZ in a lung cancer clinical trial. [ABSTRACT FROM AUTHOR]

Adenoviral (Ad) vectors in combination with the "Antigen Capsid-Incorporation" strategy have been applied in developing HIV-1 vaccines, due to the vectors׳ abilities in incorporating and inducing immunity of capsid-incorporated antigens. Variable loop 2 (V2)-specific antibodies were suggested in the RV144 trial to correlate with reduced HIV-1 acquisition, which highlights the importance of developing novel HIV-1 vaccines by targeting the V2 loop. Therefore, the V2 loop of HIV-1 has been incorporated into the Ad capsid protein. We generated adenovirus serotype 5 (Ad5) vectors displaying variable loop 2 (V2) of HIV-1 gp120, with the "Antigen Capsid-Incorporation" strategy. To assess the incorporation capabilities on hexon hypervariable region1 (HVR1) and protein IX (pIX), 20aa or full length (43aa) of V2 and V1V2 (67aa) were incorporated, respectively. Immunizations with the recombinant vectors significantly generated antibodies against both linear and discontinuous V2 epitopes. The immunizations generated durable humoral immunity against V2. This study will lead to more stringent development of various serotypes of adenovirus-vectored V2 vaccine candidates, based on breakthroughs regarding the immunogenicity of V2. [ABSTRACT FROM AUTHOR]

Viruses within human adenovirus species D (HAdV-D) infect epithelia at essentially every mucosal site. Hypervariable loops 1 and 2 of the hexon capsid protein contain epitopes that together form the epsilon determinant for serum neutralization. We report our analyses comparing HAdV-D15, 29, 56, and the recently identified type 69, each with highly similar hexons and the same serum neutralization profile, but otherwise disparate genomes. Of these, only HAdV-D type 56 is associated with epidemic keratoconjunctivitis (EKC), a severe infection of ocular surface epithelium and underlying corneal stroma. In the mouse adenovirus keratitis model, all four viruses induced inflammation. However, HAdV-D56 entry into human corneal epithelial cells and fibroblasts in vitro dramatically exceeded that of the other three viruses. We conclude that the hexon epsilon determinant is not a prime contributor to corneal tropism. [ABSTRACT FROM AUTHOR]

Adenoviruses are a ubiquitous group of viruses that have been found in a wide range of hosts. A novel adenovirus from a skunk suffering from acute hepatitis was isolated and its DNA genome sequenced. The analysis revealed this virus to be a new member of the genus Mastadenovirus , with a genome of 31,848 bp in length containing 30 genes predicted to encode proteins, and with a G+C content of 49.0%. Global genomic organization indicated SkAdV-1 was similar in organization to bat and canine adenoviruses, and phylogenetic comparison suggested these viruses shared a common ancestor. SkAdV-1 demonstrated an ability to replicate in several mammalian liver cell lines suggesting a potential tropism for this virus. [ABSTRACT FROM AUTHOR]

The Syrian golden hamster is an attractive animal for research on infectious diseases and other diseases. We report here the sequencing, assembly, and annotation of the Syrian hamster transcriptome. We include transcripts from ten pooled tissues from a naïve hamster and one stimulated with lipopolysaccharide. Our data set identified 42,707 non-redundant transcripts, representing 34,191 unique genes. Based on the transcriptome data, we generated a custom microarray and used this new platform to investigate the transcriptional response in the Syrian hamster liver following intravenous adenovirus type 5 (Ad5) infection. We found that Ad5 infection caused a massive change in regulation of liver transcripts, with robust up-regulation of genes involved in the antiviral response, indicating that the innate immune response functions in the host defense against Ad5 infection of the liver. The data and novel platforms developed in this study will facilitate further development of this important animal model. [ABSTRACT FROM AUTHOR]