Abstract

BackgroundDeer mice (Peromyscus maniculatus) are the principal reservoir hosts of Sin Nombre virus (SNV), the cause of the great majority of hantavirus cardiopulmonary syndrome (HCPS) cases in North America. SNV, like all hantaviruses with their reservoirs, causes persistent infection without pathology in deer mice and appear to elicit a regulatory T cell response. Deer mice are also susceptible to Andes virus (ANDV), which causes the great majority of HCPS cases in South America, but they clear infection by 56 days post infection without signs of disease.ResultsWe examined lymph node cell responses of deer mice infected with ANDV to determine expression profiles upon in vitro recall challenge with viral antigen. Because the deer mouse genome is currently unannotated, we developed a bioinformatics pipeline to use known lab mouse (Mus musculus) cDNAs to predict genes within the deer mouse genome and design primers for quantitative PCR (http://dna.publichealth.uga.edu/BlastPrimer/BlastPrimer.php). Of 94 genes examined, 20 were elevated, the plurality of which were Th2-specific, whereas 12 were downregulated. Other expressed genes represented Th1, regulatory T cells and follicular helper T cells, and B cells, but not Th17 cells, indicating that many cellular phenotypes participate in the host response to Andes virus.ConclusionsThe ability to examine expression levels of nearly any gene from deer mice should allow direct comparison of infection with SNV or ANDV to determine the immunological pathways used for clearance of hantavirus infection in a reservoir host species.

Highlights

  • Deer mice (Peromyscus maniculatus) are the principal reservoir hosts of Sin Nombre virus (SNV), the cause of the great majority of hantavirus cardiopulmonary syndrome (HCPS) cases in North America

  • The genus hosts a number of pathogens, including the agents that cause granulocytic ehrlichiae (Ehrlichia spp.), Lyme disease (Borrelia burgdorferi), babesiosis (Babesia microti), cryptosporidia (Cryptosporidium parvum), bartenellosis (Bartonella vinsonii), cutaneous leishmaniasis in Mexico and Central America (Leishmania mexicana), deer tick virus, Powassan virus, and Sin Nombre (SNV) and New York-1 (NYV) hantaviruses [2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17]

  • PCR array We developed software that uses BLAST of FASTAformatted cDNA sequences against sequences from the deer mouse genome to identify and assemble exons and untranslated regions into virtual deer mouse cDNAs (Figure 1)

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Summary

Introduction

Deer mice (Peromyscus maniculatus) are the principal reservoir hosts of Sin Nombre virus (SNV), the cause of the great majority of hantavirus cardiopulmonary syndrome (HCPS) cases in North America. The genus hosts a number of pathogens, including the agents that cause granulocytic ehrlichiae (Ehrlichia spp.), Lyme disease (Borrelia burgdorferi), babesiosis (Babesia microti), cryptosporidia (Cryptosporidium parvum), bartenellosis (Bartonella vinsonii), cutaneous leishmaniasis in Mexico and Central America (Leishmania mexicana), deer tick virus, Powassan virus, and Sin Nombre (SNV) and New York-1 (NYV) hantaviruses (etiologic agents of hantavirus cardiopulmonary syndrome [HCPS]) [2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17]. Reservoirs remain persistently-infected, without pathology, despite mounting an immune response that generates high-titer neutralizing antibodies within one to two months after infection [20,21,22,23]

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