Genomic organization and phylogenetic utility of deer mouse (Peromyscus maniculatus) lymphotoxin-alpha and lymphotoxin-beta

Tiffany Richens,Joseph Prescott,Aparna D~N Palmer,Tony Schountz

doi:10.1186/1471-2172-9-62

Tiffany Richens, Joseph Prescott + Show 2 more

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https://doi.org/10.1186/1471-2172-9-62

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Abstract

BackgroundDeer mice (Peromyscus maniculatus) are among the most common mammals in North America and are important reservoirs of several human pathogens, including Sin Nombre hantavirus (SNV). SNV can establish a life-long apathogenic infection in deer mice, which can shed virus in excrement for transmission to humans. Patients that die from hantavirus cardiopulmonary syndrome (HCPS) have been found to express several proinflammatory cytokines, including lymphotoxin (LT), in the lungs. It is thought that these cytokines contribute to the pathogenesis of HCPS. LT is not expressed by virus-specific CD4+ T cells from infected deer mice, suggesting a limited role for this pathway in reservoir responses to hantaviruses.ResultsWe have cloned the genes encoding deer mouse LTα and LTβ and have found them to be highly similar to orthologous rodent sequences but with some differences in promoters elements. The phylogenetic analyses performed on the LTα, LTβ, and combined data sets yielded a strongly-supported sister-group relationship between the two murines (the house mouse and the rat). The deer mouse, a sigmodontine, appeared as the sister group to the murine clade in all of the analyses. High bootstrap values characterized the grouping of murids.ConclusionNo conspicuous differences compared to other species are present in the predicted amino acid sequences of LTα or LTβ; however, some promoter differences were noted in LTβ. Although more extensive taxonomic sampling is required to confirm the results of our analyses, the preliminary findings indicate that both genes (analyzed both separately and in combination) hold potential for resolving relationships among rodents and other mammals at the subfamily level.

Highlights

Deer mice (Peromyscus maniculatus) are among the most common mammals in North America and are important reservoirs of several human pathogens, including Sin Nombre hantavirus (SNV)
Hantavirus cardiopulmonary syndrome (HCPS) is caused by several pathogenic New World hantaviruses, but most North American cases of hantavirus cardiopulmonary syndrome (HCPS) are caused by Sin Nombre virus (SNV) [2,3,4,5]
D48 in the A'-A" loop and Y106 in the D-E loop involved in binding to TNFR1 [14] are conserved in deer mouse LTα

Summary

Introduction

Deer mice (Peromyscus maniculatus) are among the most common mammals in North America and are important reservoirs of several human pathogens, including Sin Nombre hantavirus (SNV). Patients that die from hantavirus cardiopulmonary syndrome (HCPS) have been found to express several proinflammatory cytokines, including lymphotoxin (LT), in the lungs. The principal reservoir host of SNV, the deer mouse (Peromyscus maniculatus) [7], exhibits no conspicuous pathology and remains persistently infected for life [8,9]. It is unknown how deer mice can be persistently infected without pathology because few methods have been developed for characterizing cytokine responses in this species. We previously reported a partial cDNA sequence of deer mouse LTα [10] and present here genomic, structural, and phylogenetic characterizations of the complete lymphotoxin genes

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