Viral pathogenesis in mice is similar for West Nile virus derived from mosquito and mammalian cells

Lim, Pei-Yin; Louie, Karen L.; Styer, Linda M.; Shi, Pei–Yong; Bernard, Kristen A.

doi:10.1016/j.virol.2010.01.029

Cited by 20 publications

(27 citation statements)

References 41 publications

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“…Interestingly, studies with cell culture have suggested that flavivirus propagated in mosquito cells could differentially modulate innate immune responses from virus grown in mammalian cells (2,40). However, this conclusion was not supported by pathogenesis studies with mice (11,25).…”

Section: Discussionmentioning

confidence: 99%

Pivotal Role of Antibody and Subsidiary Contribution of CD8⁺T Cells to Recovery from Infection in a Murine Model of Japanese Encephalitis

Larena

Regner

Lee

et al. 2011

J Virol

119

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Section: Discussionmentioning

confidence: 99%

Pivotal Role of Antibody and Subsidiary Contribution of CD8⁺T Cells to Recovery from Infection in a Murine Model of Japanese Encephalitis

Larena

Regner

Lee

et al. 2011

J Virol

119

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“…Virus was produced from a full-length cDNA clone of a WNV isolate obtained from New York, NY, in 2000 (25). RNA was transcribed in vitro from the cDNA clone and electroporated into BHK-21 or C6/36 cells as previously described (14). The viral stocks were designated WNV-BHK for virus harvested from BHK-21 cells and WNV-C6/36 for virus harvested from C6/36 cells.…”

Section: Methodsmentioning

confidence: 99%

“…We therefore determined whether spot feeding lowers the infectious dose of WNV by enhancing early infection. The ID 50 of needle-inoculated WNV in our mouse model is approximately 1 PFU (14). Thus, we inoculated 1 or 10 PFU of WNV with and without spot feeding.…”

Section: Vol 85 2011 Mosquito Saliva Enhances West Nile Virus Infecmentioning

confidence: 99%

Mosquito Saliva Causes Enhancement of West Nile Virus Infection in Mice

Styer

Lim

Louie

et al. 2011

J Virol

Self Cite

162

179

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West Nile virus (WNV) is transmitted to vertebrate hosts primarily by infected Culex mosquitoes. Transmission of arboviruses by the bite of infected mosquitoes can potentiate infection in hosts compared to viral infection by needle inoculation. Here we examined the effect of mosquito transmission on WNV infection and systematically investigated multiple factors that differ between mosquito infection and needle inoculation of WNV. We found that mice infected with WNV through the bite of a single infected Culex tarsalis mosquito exhibited 5-to 10-fold-higher viremia and tissue titers at 24 and 48 h postinoculation and faster neuroinvasion than mice given a median mosquito-inoculated dose of WNV (10 5 PFU) by needle. Mosquito-induced enhancement was not due to differences in inoculation location, because additional intravenous inoculation of WNV did not enhance viremia or tissue titers. Inoculation of WNV into a location where uninfected mosquitoes had fed resulted in enhanced viremia and tissue titers in mice similar to those in mice infected by a single infected mosquito bite, suggesting that differences in where virus is deposited in the skin and in the virus particle itself were not responsible for the enhanced early infection in mosquito-infected mice. In addition, inoculation of mice with WNV mixed with salivary gland extract (SGE) led to higher viremia, demonstrating that mosquito saliva is the major cause of mosquito-induced enhancement. Enhanced viremia was not observed when SGE was inoculated at a distal site, suggesting that SGE enhances WNV replication by exerting a local effect. Furthermore, enhancement of WNV infection still occurred in mice with antibodies against mosquito saliva. In conclusion, saliva from C. tarsalis is responsible for enhancement of early WNV infection in vertebrate hosts.

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“…Functional type I IFN in sera was measured as described previously (22). Briefly, serum samples and standards (recombinant mouse IFN-␤; Chemicon International, Temecula, CA) were diluted in complete medium, treated with 2 N HCl, and incubated at 4°C overnight.…”

Section: Cellsmentioning

confidence: 99%

Nonconsensus West Nile Virus Genomes Arising during Mosquito Infection Suppress Pathogenesis and Modulate Virus Fitness In Vivo

Ebel

Fitzpatrick

Lim

et al. 2011

J Virol

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West Nile virus (WNV) is similar to other RNA viruses in that it forms genetically complex populations within hosts. The virus is maintained in nature in mosquitoes and birds, with each host type exerting distinct influences on virus populations. We previously observed that prolonged replication in mosquitoes led to increases in WNV genetic diversity and diminished pathogenesis in mice without remarkable changes to the consensus genome sequence. We therefore sought to evaluate the relationships between individual and group phenotypes in WNV and to discover novel viral determinants of pathogenesis in mice and fitness in mosquitoes and birds. Individual plaque size variants were isolated from a genetically complex population, and mutations conferring a small-plaque and mouse-attenuated phenotype were localized to the RNA helicase domain of the NS3 protein by reverse genetics. The mutation, an Asp deletion, did not alter type I interferon production in the host but rendered mutant viruses more susceptible to interferon compared to wild type (WT) WNV. Finally, we used an in vivo fitness assay in Culex quinquefasciatus mosquitoes and chickens to determine whether the mutation in NS3 influenced fitness. The fitness of the NS3 mutant was dramatically lower in chickens and moderately lower in mosquitoes, indicating that RNA helicase is a major fitness determinant of WNV and that the effect on fitness is host specific. Overall, this work highlights the complex relationships that exist between individual and group phenotypes in RNA viruses and identifies RNA helicase as an attenuation and fitness determinant in WNV.West Nile virus (WNV; Flaviviridae: Flavivirus) is a positivesense, single-stranded RNA (ssRNA) virus belonging to the Japanese encephalitis virus (JEV) serological complex of the flaviviruses. WNV perpetuates in nature in enzootic transmission cycles through alternating replication in (mainly avian) vertebrates and mosquitoes. The specific mosquito and avian hosts that are most important in a particular locality differ but tend to include Culex species mosquitoes and passerine birds (2, 10). WNV infection of mammals, including humans and horses, occurs via spillover from this enzootic cycle. Since its introduction into North America in 1999 (20), molecular epidemiologic studies have clearly demonstrated that the virus has evolved to maximize its transmission potential within local transmission cycles (8,11,23). This finding stimulated subsequent efforts to understand the details of the underlying evolutionary mechanisms that lead to population-level genetic and phenotypic changes in the virus. In brief, these studies demonstrated that WNV populations are genetically diverse within hosts (15), that genetic diversity may be shared between hosts (15), and that mosquito infection drives genetic diversification of the virus population both through relaxation of purifying selection and through selection of rare genotypes resulting from RNA interference (RNAi) (4,16,17). Thus, in the WNV transmission cycle, different...

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Viral pathogenesis in mice is similar for West Nile virus derived from mosquito and mammalian cells

Cited by 20 publications

References 41 publications

Pivotal Role of Antibody and Subsidiary Contribution of CD8⁺T Cells to Recovery from Infection in a Murine Model of Japanese Encephalitis

Pivotal Role of Antibody and Subsidiary Contribution of CD8⁺T Cells to Recovery from Infection in a Murine Model of Japanese Encephalitis

Mosquito Saliva Causes Enhancement of West Nile Virus Infection in Mice

Nonconsensus West Nile Virus Genomes Arising during Mosquito Infection Suppress Pathogenesis and Modulate Virus Fitness In Vivo

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Viral pathogenesis in mice is similar for West Nile virus derived from mosquito and mammalian cells

Cited by 20 publications

References 41 publications

Pivotal Role of Antibody and Subsidiary Contribution of CD8+T Cells to Recovery from Infection in a Murine Model of Japanese Encephalitis

Pivotal Role of Antibody and Subsidiary Contribution of CD8+T Cells to Recovery from Infection in a Murine Model of Japanese Encephalitis

Mosquito Saliva Causes Enhancement of West Nile Virus Infection in Mice

Nonconsensus West Nile Virus Genomes Arising during Mosquito Infection Suppress Pathogenesis and Modulate Virus Fitness In Vivo

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Pivotal Role of Antibody and Subsidiary Contribution of CD8⁺T Cells to Recovery from Infection in a Murine Model of Japanese Encephalitis

Pivotal Role of Antibody and Subsidiary Contribution of CD8⁺T Cells to Recovery from Infection in a Murine Model of Japanese Encephalitis