Persistent Seoul virus infection in Lewis rats

Abstract

Mechanistic studies of hantavirus persistence in rodent reservoirs have been limited by the lack of a versatile animal model. This report describes findings from experimental infection of inbred Lewis rats with Seoul virus strain 80-39. Rats inoculated with virus intraperitoneally at 6 days of age became persistently infected without clinical signs. Tissues from Seoul virus-inoculated 6-day-old rats were assessed at 6, 9, and 12 weeks post-inoculation for viral RNA by RT-PCR and in situ hybridization (ISH) and for infectious virus by inoculation of Vero E6 cells. Virus was isolated from lung and kidney of infected rats at 6 weeks and viral RNA was detected in lung, kidney, pancreas, salivary gland, brain, spleen, liver and skin at 6, 9 and 12 weeks. Rats inoculated with Seoul virus intraperitoneally at 10 or 21 days of age became infected without clinical signs but had low to undetectable levels of viral RNA in tissues at 6 weeks post-inoculation. ISH identified vascular smooth muscle and endothelial cells as common sites of persistent infection. Cultured rat smooth muscle cells and to a lesser extent cultured endothelial cells also were susceptible to Seoul virus infection. Pancreatic infection resulted in insulitis with associated hyperglycemia. These studies demonstrate that infant Lewis rats are uniformly susceptible to asymptomatic persistent Seoul virus infection. Additionally, they offer opportunities for correlative in vivo and in vitro study of Seoul virus interactions in host cell types that support persistent infection.

Hantavirus‐specific IgA in saliva and viral antigen in the parotid gland in patients with hemorrhagic fever with renal syndrome

“…The findings indicate that virus found in saliva can be the result of shedding from the salivary gland. Presence of hantavirus antigen in the human salivary glands has not previously been published, but hantavirus antigen in rodent and mouse salivary glands has been demonstrated [Lee et al, 1981; Botten et al, 2000; Compton et al, 2004]. Hantavirus is infectious in rodent saliva and experimental studies with sigmodontine rodents hosting ANDV have investigated the hypothesis that saliva is one of the sources of infection within reservoir populations [Padula et al, 2004].…”

Treatment of hantavirus pulmonary syndrome

“…They include traditional laboratory animals, such as mice, hamsters, macaques, and natural rodent hosts of hantavirus infection, such as bank voles, cotton rats and deer mice. Models involving natural rodent hosts show persistent, life-long infections (Botten et al, 2003;Compton et al, 2004;Tanishita et al, 1986). In contrast, models utilizing mice, rats, gerbils, and nonhuman primates involve acute infection, which may be asymptomatic (Kurata et al, 1983;Xu et al, 1992;Schmaljohn et al, 1990) or, in the recently described hamster model, involve lethal disease (Hooper et al, 2001b).…”

Viral Disease

“…Most studies of Seoul virus pathology in rats have used experimental intraperitoneal inoculation (Compton et al, 2004;Lee et al, 1986). In 1-to 7-day-old rats inoculated with Seoul virus, infection of the central nervous system can lead to ataxia, limb paralysis, tremors, and in some cases death 2e3 weeks postinoculation (Compton et al, 2004;Mori et al, 1991;Zhang et al, 1989).…”