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

We established a colony of SNV antibody-negative deer mice and cloned 11 cytokine and chemokine partial cDNA sequences using directed PCR. Most of the deer mouse sequences were highly conserved with orthologous sequences from other rodent species and functional domains were identified in each putative polypeptide.The availability of these sequences will allow the examination of the role of these cytokines in deer mouse responses to infection with Sin Nombre virus.Deer mice (Peromyscus maniculatus) are the principal natural host of Sin Nombre virus (SNV), the etiologic agent of most hantavirus pulmonary syndrome (HPS) cases in humans in North America [1-3]. Deer mice are found throughout most of North America, except for the eastern seaboard and southeast United States [4].SNV predominantly infects capillary endothelial cells without discernible pathology [5]. A prominent feature of HPS is capillary leakage and subsequent hypotension that causes death by cardiac failure. In addition to resident alveolar macrophages, lymphocytes infiltrate the lungs of patients and contribute to the pathology by secreting proinflammatory cytokines, including interferon-γ (IFNγ), interleukin-2 (IL-2), tumor necrosis factor (TNF), and lymphotoxin (LT) [6]. These characteristics suggest HPS may be a cytokine-mediated immunopathology.As is usual with most long-term reservoir hosts, deer mice exhibit little pathology during acute infection with SNV [7]. The virus infects capillary endothelial cells of deer mouse lungs, but lymphocyte infiltration or inflammation are not observed. After acute infection, the virus establishes persistence in many tissues [8] and most, if not all, deer mice remain infected for the remainders of their lives.The role of the immune response in infected deer mice is unclear because few reagents of defined specificity have been developed to characterize their immune function. A strong IgG antibody response occurs [7,9], suggesting that B cells and helper T cells pa