Shedding and Intracage Transmission of Sin Nombre Hantavirus in the Deer Mouse ( Peromyscus maniculatus ) Model

Abstract

The mechanism(s) by which Sin Nombre (SN) hantavirus is maintained in deer mouse populations is unclear. Field studies indicate that transmission occurs primarily if not exclusively via a horizontal mechanism. Using an experimental deer mouse infection model in an outdoor laboratory, we tested whether infected rodents shed SN virus in urine, feces, and saliva, whether infected mice transmit infection to naïve cage mates, and whether infected dams are able to vertically transmit virus or antibody to offspring. Using pooled samples of urine, feces, and saliva collected from mice infected 8 to 120 days postinoculation (p.i.), we found that a subset of saliva samples, collected between 15 and 90 days p.i., contained viral RNA. Parallel studies conducted on wild-caught, naturally infected deer mice showed a similar pattern of intermittent positivity, also only in saliva samples. Attempts to isolate virus through inoculation of cells or naïve deer mice with the secreta or excreta of infected mice were uniformly negative. Of 54 attempts to transmit infection by cohousing infected deer mice with seronegative cage mates, we observed only a single case of transmission, which occurred between 29 and 42 days p.i. Dams passively transferred antibodies to neonatal pups via milk, and those antibodies persisted for at least 2 months after weaning, but none transmitted infection to their pups. Compared to other hantavirus models, SN virus is shed less efficiently and transmits inefficiently among cage mates. Transmission of SN virus among reservoir rodents may require factors that are not required for other hantaviruses.Hantaviruses (Bunyaviridae family; Hantavirus genus) are rodent-borne viruses with a worldwide distribution. As with other members of the family Bunyaviridae, hantaviruses are enveloped and have a tripartite, negative-sense RNA genome. Two distinct human illnesses are associated with hantavirus infection: hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome (HCPS) (36). HFRS occurs primarily in Europe and Asia, with a case/fatality ratio of 0.1 to 10% (36). Etiologic agents of HFRS include the prototypic Hantaan (HTN) virus, Seoul (SEO) virus, Puumala (PUU) virus, and Dobrava-Belgrade virus. HCPS occurs in North and South America (28). There are at least four etiologic agents of HCPS in North America: Sin Nombre (SN), Bayou, New York, and Black Creek Canal (BCC) viruses. Of these four viruses, the primary etiologic agent is SN virus, which is believed to be responsible for a large majority (Ͼ95%) of the more than 300 reported cases. The case/fatality ratio of HCPS is approximately 40%. The deer mouse (Peromyscus maniculatus) is the predominant carrier of SN virus (12,32).Natural transmission of hantaviruses among wild rodents is poorly understood, but both field and laboratory studies suggest that nearly all, if not all, transmission is via one or more horizontal routes and that male mice are differentially affected.In this study, we tested the hypothesis that deer mice experimenta...

Long-Term Dynamics of Sin Nombre Viral Rna and Antibody in Deer Mice in Montana

“…These results are concordant with findings by Botten et al (2000), who also found this stage of infection to be transient or rarely detected. Netski et al (1999) found that SNV antigen concentrations were highest in the kidneys of wild-caught deer mice that had no antibody to SNV but had SNV RNA in the blood (those that they presumed to have been infected very recently).…”

“…Other studies suggest that hantaviral replication in tissues is variable during chronic infection; intervals of virus shedding in urine, feces, and saliva and intermittent presence of viral RNA or even infectious virus in blood can be expected (Hutchinson et al, 1998;Botten et al, 2002). A second possible explanation for the alternating nature of viral RNA is viral recrudescence.…”

“…Under various forms of stress, including immunosuppression, immunologic dyscrasias, malignancies,heat,cold,shock,pregnancy,etc.,herpesviruses,Hepatitis B virus,Hepatitis C virus,B19 virus, and other viruses may be reactivated (Halford et al, 1996;Mehta et al, 2004). The SNV reactivation in deer mice due to seasonal influences or immunosuppression has been suggested (Botten et al, 2002) and replication of Seoul virus appears to be much faster in the immunosuppressed nude rat than in normal rats (Dohme et al, 1994). The exact initiating causes of recrudescence in these cases are unclear.…”

“…Laboratory studies have demonstrated a consistent pattern of events following hantavirus infections of their natural rodent hosts (Lee et al, 1981;Yanagihara et al, 1985;Gavrilovskaya et al, 1990;Hutchinson et al, 1998;Botten et al, 2000Botten et al, , 2003. First, there is a brief viremia, followed by the development of circulating antibody, and then consequent clearance of virus from the blood.…”

Rapid and Simple Method for Screening Wild Rodents for Antibodies to Sin Nombre Hantavirus

“…Prevalence of anti-SNV IgG in wild deer mice is highest in those Ͻ10.9 g mass, declines in mice Ն10.9-Յ14.3 g, and increases in those Ͼ14.3 g. The group of small mice probably acquired anti-SNV antibodies passively through the placenta and the decline in seroprevalence between birth and 14.3 g is thought to be due to attrition of maternal antibodies (Mills et al, 1997). Additional experimental evidence has continued to accrue demonstrating that specific anti-hantavirus IgG antibodies can be passed through the placenta and may be protective from challenge by SNV (Borucki et al, 2000;Camaioni, 2001;Botten et al, 2002).…”