Cloning and characterization of deer mouse (Peromyscus maniculatus) cytokine and chemokine cDNAs

Schountz, Tony; Green, Renata; Davenport, Bennett; Buniger, Amie; Richens, Tiffany R.; Root, J. Jeffrey; Davidson, Forbes; Calisher, Charles H.; Beaty, Barry J.

doi:10.1186/1471-2172-5-1

Cited by 24 publications

(8 citation statements)

References 42 publications

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“…Experimental infection of natural hosts with hantaviruses have earlier been established for Sin Nombre virus (SNV), Seoul virus and PUUV [14] , [25] – [27] . In addition, genes encoding deer mouse chemokines and cytokines have been sequenced [28] , [29] , thereby enabling studies of immune responses during SNV-infection of the natural host in vivo . However, to our knowledge this is the first report of an in vitro -model based on cells from a natural hantavirus host.…”

Section: Discussionmentioning

confidence: 99%

A Model System for In Vitro Studies of Bank Vole Borne Viruses

et al. 2011

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The bank vole (Myodes glareolus) is a common small mammal in Europe and a natural host for several important emerging zoonotic viruses, e.g. Puumala hantavirus (PUUV) that causes hemorrhagic fever with renal syndrome (HFRS). Hantaviruses are known to interfere with several signaling pathways in infected human cells, and HFRS is considered an immune-mediated disease. There is no in vitro-model available for infectious experiments in bank vole cells, nor tools for analyses of bank vole immune activation and responses. Consequently, it is not known if there are any differences in the regulation of virus induced responses in humans compared to natural hosts during infection. We here present an in vitro-model for studies of bank vole borne viruses and their interactions with natural host cell innate immune responses. Bank vole embryonic fibroblasts (VEFs) were isolated and shown to be susceptible for PUUV-infection, including a wild-type PUUV strain (only passaged in bank voles). The significance of VEFs as a model system for bank vole associated viruses was further established by infection studies showing that these cells are also susceptible to tick borne encephalitis, cowpox and Ljungan virus. The genes encoding bank vole IFN-β and Mx2 were partially sequenced and protocols for semi-quantitative RT-PCR were developed. Interestingly, PUUV did not induce an increased IFN-β or Mx2 mRNA expression. Corresponding infections with CPXV and LV induced IFN-β but not Mx2, while TBEV induced both IFN-β and Mx2.In conclusion, VEFs together with protocols developed for detection of bank vole innate immune activation provide valuable tools for future studies of how PUUV and other zoonotic viruses affect cells derived from bank voles compared to human cells. Notably, wild-type PUUV which has been difficult to cultivate in vitro readily infected VEFs, suggesting that embryonic fibroblasts from natural hosts might be valuable for isolation of wild-type hantaviruses.

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Section: Discussionmentioning

confidence: 99%

A Model System for In Vitro Studies of Bank Vole Borne Viruses

et al. 2011

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“…40; unpublished observations). Consequently, we developed molecular assays to overcome these limitations (35,41,42).…”

Section: Discussionmentioning

confidence: 99%

Regulatory T cell-like responses in deer mice persistently infected with Sin Nombre virus

Schountz

Prescott²,

Cogswell³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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107

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Hantavirus cardiopulmonary syndrome is a zoonotic illness associated with a systemic inflammatory immune response, capillary leak, noncardiogenic pulmonary edema, and shock in humans. Cytokines, including TNF, IFN-␥, and lymphotoxin, are thought to contribute to its pathogenesis. In contrast, infected rodent reservoirs of hantaviruses experience few or no pathologic changes and the host rodent can remain persistently infected for life. Generally, it is unknown why such dichotomous immune responses occur between humans and reservoir hosts. Thus, we examined CD4 ؉ T cell responses from one such reservoir, the deer mouse (Peromy-

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“…Deer mice ( Peromyscus maniculatus nebrascensis ) of both sexes and of 6 months of age were kindly provided by Dr. Ann Hawkinson at the University of Northern Colorado. This colony was established with deer mice captured near Whitewater, CO in 2000 ( 34 ). All animal work was approved by the Colorado State University Institutional Animal Care and Use Committee (protocol #993).…”

Section: Methodsmentioning

confidence: 99%

SARS-CoV-2 infection, neuropathogenesis and transmission among deer mice: Implications for reverse zoonosis to New World rodents

Fagre

Lewis

Eckley

et al. 2020

Preprint

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Coronavirus disease-19 (COVID-19) emerged in November, 2019 in China and rapidly became pandemic. As with other coronaviruses, a preponderance of evidence suggests the virus originated in horseshoe bats (Rhinolophus spp.) and likely underwent a recombination event in an intermediate host prior to entry into human populations. A significant concern is that SARS-CoV-2 could become established in secondary reservoir hosts outside of Asia. To assess this potential, we challenged deer mice (Peromyscus maniculatus) with SARS-CoV-2 and found robust virus replication in the upper respiratory tract, lungs and intestines, with detectable viral RNA for up to 21 days in oral swabs and 14 days in lungs. Virus entry into the brain also occurred, likely via gustatory-olfactory-trigeminal pathway with eventual compromise to the blood brain barrier. Despite this, no conspicuous signs of disease were observed and no deer mice succumbed to infection. Expression of several innate immune response genes were elevated in the lungs, notably IFNα, Cxcl10, Oas2, Tbk1 and Pycard. Elevated CD4 and CD8β expression in the lungs was concomitant with Tbx21, IFNγ and IL-21 expression, suggesting a type I inflammatory immune response. Contact transmission occurred from infected to naive deer mice through two passages, showing sustained natural transmission. In the second deer mouse passage, an insertion of 4 amino acids occurred to fixation in the N-terminal domain of the spike protein that is predicted to form a solvent-accessible loop. Subsequent examination of the source virus from BEI Resources indicated the mutation was present at very low levels, demonstrating potent purifying selection for the insert during in vivo passage. Collectively, this work has determined that deer mice are a suitable animal model for the study of SARS-CoV-2 pathogenesis, and that they have the potential to serve as secondary reservoir hosts that could lead to periodic outbreaks of COVID-19 in North America.

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Cloning and characterization of deer mouse (Peromyscus maniculatus) cytokine and chemokine cDNAs

Cited by 24 publications

References 42 publications

A Model System for In Vitro Studies of Bank Vole Borne Viruses

A Model System for In Vitro Studies of Bank Vole Borne Viruses

Regulatory T cell-like responses in deer mice persistently infected with Sin Nombre virus

SARS-CoV-2 infection, neuropathogenesis and transmission among deer mice: Implications for reverse zoonosis to New World rodents

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