The relationship between hantaviruses and their reservoir hosts is not well understood. We successfully passaged a mouse-adapted strain of Sin Nombre virus from deer mice (Peromyscus maniculatus) by i.m. inoculation of 4-to 6-wk-old deer mouse pups. After inoculation with 5 ID50, antibodies to the nucleocapsid (N) antigen first became detectable at 14 d whereas neutralizing antibodies were detectable by 7 d. Viral N antigen first began to appear in heart, lung, liver, spleen, and͞or kidney by 7 d, whereas viral RNA was present in those tissues as well as in thymus, salivary gland, intestine, white fat, and brown fat. By 14 d nearly all tissues examined displayed both viral RNA and N antigen. We noted no consistent histopathologic changes associated with infection, even when RNA load was high. Viral RNA titers peaked on 21 d in most tissues, then began to decline by 28 d. Infection persisted for at least 90 d. The RNA titers were highest in heart, lung, and brown fat. Deer mice can be experimentally infected with Sin Nombre virus, which now allows provocative examination of the virus-host relationship. The prominent involvement of heart, lung, and brown fat suggests that these sites may be important tissues for early virus replication or for maintenance of the virus in nature.

The immunologic responses that mediate viral clearance of and recovery from hantavirus cardiopulmonary syndrome (HCPS) due to Sin Nombre (SN) virus are unknown. Serial serum samples from 26 patients with acute SN virus infection were tested for IgG, IgA, and IgM reactivity to recombinant viral nucleocapsid (N) and glycoprotein G1 antigens by a novel strip immunoblot assay. The titers of antibodies capable of neutralizing SN virus in vitro also were determined for each sample. At admission, patients with severe disease had lower titers of IgG antibodies to SN virus N antigen (P<.033) and lower neutralizing antibody titers (P<3.4x10-5), compared with patients with mild disease. These data suggest that a strong neutralizing antibody response may be a predictor of effective clearance of and recovery from SN virus infection and raise the possibility that passive immunotherapy may be useful in HCPS.

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