Transcriptome sequencing and development of an expression microarray platform for liver infection in adenovirus type 5-infected Syrian golden hamsters

Bai, Ying; Tóth, Károly; Spencer, Jacqueline F.; Aurora, Rajeev; Wold, William S.M.

doi:10.1016/j.virol.2015.07.024

Cited by 20 publications

(22 citation statements)

References 73 publications

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“…injection of Ad5. We found that about 20% of transcripts were up-or downregulated, with prominent upregulation of genes involved in the innate immune response to virus infection (36). The latter finding is consistent with our recent study in Syrian hamsters with the STAT2 gene knocked out (STAT2 KO hamsters).…”

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confidence: 92%

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Pathology in Permissive Syrian Hamsters after Infection with Species C Human Adenovirus (HAdV-C) Is the Result of Virus Replication: HAdV-C6 Replicates More and Causes More Pathology than HAdV-C5

Tollefson

Bai

Spencer

et al. 2017

J Virol

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Syrian hamsters are permissive for the replication of species C human adenoviruses (HAdV-C). The virus replicates to high titers in the liver of these animals after intravenous infection, while respiratory infection results in virus replication in the lung. Here we show that two types belonging to species C, HAdV-C5 and HAdV-C6, replicate to significantly different extents and cause pathology with significantly different severities, with HAdV-C6 replicating better and inducing more severe and more widespread lesions. The virus burdens in the livers of HAdV-C6-infected hamsters are higher than the virus burdens in HAdV-C5-infected ones because more of the permissive hepatocytes get infected. Furthermore, when hamsters are infected intravenously with HAdV-C6, live, infectious virus can be isolated from the lung and the kidney, which is not seen with HAdV-C5. Similarly to mouse models, in hamsters, HAdV-C6 is sequestered by macrophages to a lesser degree than HAdV-C5. Depletion of Kupffer cells from the liver greatly increases the replication of HAdV-C5 in the liver, while it has only a modest effect on the replication of HAdV-C6. Elimination of Kupffer cells also dramatically increases the pathology induced by HAdV-C5. These findings indicate that in hamsters, pathology resulting from intravenous infection with adenoviruses is caused mostly by replication in hepatocytes and not by the abortive infection of Kupffer cells and the following cytokine storm. Immunocompromised human patients can develop severe, often lethal adenovirus infections. Respiratory adenovirus infection among military recruits is a serious problem, in some cases requiring hospitalization of the patient. Furthermore, adenovirus-based vectors are frequently used as experimental viral therapeutic agents. Thus, it is imperative that we investigate the pathogenesis of adenoviruses in a permissive animal model. Syrian hamsters are susceptible to infection with certain human adenoviruses, and the pathology accompanying these infections is similar to what is observed with adenovirus-infected human patients. We demonstrate that replication in permissive cells in a susceptible host animal is a major part of the mechanism by which systemic adenovirus infection induces pathology, as opposed to the chiefly immune-mediated pathology observed in nonsusceptible hosts. These findings support the use of compounds inhibiting adenovirus replication as a means to block adenovirus-induced pathology.

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confidence: 92%

“…To further develop the Syrian hamster as a model, we (36) and others (37) have sequenced the Syrian hamster transcriptome. We identified 42,707 unique transcripts representing 34,191 unique genes.…”

mentioning

confidence: 99%

Pathology in Permissive Syrian Hamsters after Infection with Species C Human Adenovirus (HAdV-C) Is the Result of Virus Replication: HAdV-C6 Replicates More and Causes More Pathology than HAdV-C5

Tollefson

Bai

Spencer

et al. 2017

J Virol

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“…Although the historical lack of immune reagents for hamsters has resulted in a relatively poor understanding of basic hamster immunology, a number of recently developed research tools—including the hamster transcriptome and kinome4748, microarray platforms49, and RT-qPCR assays to measure the host response17—are poised to increase the value of hamsters as an animal model. In addition, together with the EHF hamster model, the MHF hamster model will contribute to both basic and translational research for the development of medical countermeasures such as pan-filovirus therapies and bivalent vaccines.…”

Section: Discussionmentioning

confidence: 99%

A hamster model for Marburg virus infection accurately recapitulates Marburg hemorrhagic fever

Marzi

Banadyga

Haddock

et al. 2016

Sci Rep

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Marburg virus (MARV), a close relative of Ebola virus, is the causative agent of a severe human disease known as Marburg hemorrhagic fever (MHF). No licensed vaccine or therapeutic exists to treat MHF, and MARV is therefore classified as a Tier 1 select agent and a category A bioterrorism agent. In order to develop countermeasures against this severe disease, animal models that accurately recapitulate human disease are required. Here we describe the development of a novel, uniformly lethal Syrian golden hamster model of MHF using a hamster-adapted MARV variant Angola. Remarkably, this model displayed almost all of the clinical features of MHF seen in humans and non-human primates, including coagulation abnormalities, hemorrhagic manifestations, petechial rash, and a severely dysregulated immune response. This MHF hamster model represents a powerful tool for further dissecting MARV pathogenesis and accelerating the development of effective medical countermeasures against human MHF.

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“…HapT1 cells were incubated with FITC-conjugated anti-mouse/rat MHC Class II antibody (I-Ek; clone 14-4-4 S, eBioscience) 49 for 1 h and fixed in 4% paraformaldehyde for 5 min, and analyzed on BD Accuri C6.…”

Section: Flow Cytometric Analysesmentioning

confidence: 99%

Syngeneic Syrian hamster tumors feature tumor-infiltrating lymphocytes allowing adoptive cell therapy enhanced by oncolytic adenovirus in a replication permissive setting

et al. 2016

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Adoptive transfer of tumor-infiltrating lymphocytes (TIL) has shown promising yet sometimes suboptimal results in clinical trials for advanced cancer, underscoring the need for approaches improving efficacy and safety. Six implantable syngeneic tumor cell lines of the Syrian hamster were used to initiate TIL cultures. TIL generated from tumor fragments cultured in human interleukin-2 (IL-2) for 10 d were adoptively transferred into tumorbearing hamsters with concomitant intratumoral injections of oncolytic adenovirus (Ad5-D24) for the assessment of antitumor efficacy. Pancreatic cancer (HapT1) and melanoma (RPMI 1846) TIL exhibited potent and tumor-specific cytotoxicity in effector-to-target (E/T) assays. MHC Class I blocking abrogated the cell killing of RPMI 1846 TIL, indicating cytotoxic CD8 C T-cell activity. When TIL were combined with Ad5-D24 in vitro, HapT1 tumor cell killing was significantly enhanced over single agents. In vivo, the intratumoral administration of HapT1 TIL and Ad5-D24 resulted in improved tumor growth control compared with either treatment alone. Additionally, splenocytes derived from animals treated with the combination of Ad5-D24 and TIL killed autologous tumor cells more efficiently than monotherapy-derived splenocytes, suggesting that systemic antitumor immunity was induced. For the first time, TIL of the Syrian hamster have been cultured, characterized and used therapeutically together with oncolytic adenovirus for enhancing the efficacy of TIL therapy. Our results support human translation of oncolytic adenovirus as an enabling technology for adoptive T-cell therapy of solid tumors.

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Transcriptome sequencing and development of an expression microarray platform for liver infection in adenovirus type 5-infected Syrian golden hamsters

Cited by 20 publications

References 73 publications

Pathology in Permissive Syrian Hamsters after Infection with Species C Human Adenovirus (HAdV-C) Is the Result of Virus Replication: HAdV-C6 Replicates More and Causes More Pathology than HAdV-C5

Pathology in Permissive Syrian Hamsters after Infection with Species C Human Adenovirus (HAdV-C) Is the Result of Virus Replication: HAdV-C6 Replicates More and Causes More Pathology than HAdV-C5

A hamster model for Marburg virus infection accurately recapitulates Marburg hemorrhagic fever

Syngeneic Syrian hamster tumors feature tumor-infiltrating lymphocytes allowing adoptive cell therapy enhanced by oncolytic adenovirus in a replication permissive setting

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