Pathogenesis of Hantaan Virus in Mice

Abstract

SUMMARYThe virulence of two virus clones (HV cl-I and HV cl-2) of Hantaan virus, which were plaque-purified on Vero E6 cells, were compared in suckling mice infected by the intraperitoneal or intracerebral route. HV cl-1 increased the mortality of the mice whereas HV cl-2 did not. Furthermore, virus of high titre was isolated from various organs of mice infected with HV cl-1 and high titres were maintained, whereas after infection with HV cl-2, virus was isolated from various organs only in low titre and only temporarily. HV cl-1 strongly induced cell-to-cell fusion, but the cell fusion activity was at a minimum level in cells infected with HV cl-2. However these two clones induced similar titres of antibodies in mice. Cytotoxic T lymphocyte assays against macrophages infected with homologous and heterologous virus showed that cytotoxic T cell activity was induced in mice infected with HV cl-2, but suppressed in mice infected with HV cl-1. These results suggest that an alteration in the cell fusion function and the cytotoxic T cell activity are important in the pathogenesis of Hantaan virus infection in newborn mice.

Hantavirus Infection in SCID Mice.

“…However, previous reports of experimental infection of newborn mice showed that virus isolation was successful within 1 week p.i. [21]. However, SCID mice inoculated with HTN seemed not to have become infectious until at least 2 weeks p.i.…”

“…Various animal experiments have been carried out to examine the mechanisms which regulate the pathogenicity of hantavirus to rodents, and to examine the availability of an animal model for HFRS [7,8,14,20,24]. Systemic infection leading to lethal outcome was observed only among newborn mice [15,21], newborn rats [30] and nude rats [6] which have immature or defective immune systems. Passive cell transfer from immunocompetent mice conferred passive protection to newborn mice, indicating an important role for host immunity in hantavirus protection.…”

Microbiological Contamination of Laboratory Mice and Rats in Korea from 1999 to 2003

“…Hantavirus is not a microbiological monitoring item at the ICLAS Monitoring Center for mice [10,17], but on the basis of our data, hantavirus could be recommended as one of the important pathogens selected for microbiological moni- toring in mice in Korea. Hantavirus has been isolated from wild-caught Mus musculus [1], and Hantaan virus, the prototype of the genus Hantavirus, caused lethal encephalitis in adult immunocompetent laboratory mice [16] and symptomatic infection in newborn mice [3,11,15,18]. Among the zoonotic or fatal pathogens of rats, only Sendai virus was present in rat facilities with the barrier system.…”

Comparison of Virulence between Seoul Virus Strain SR‐11 and Hantaan Virus Strain 76–118 of Hantaviruses in Newborn Mice

“…The present study confirmed that strain SR-11 used here possessed much higher virulence to newborn mice than that to newborn rats. Moreover, it has been shown from several animal experiments that strain HTN required more than 100 PFU of inoculum to cause 100% lethality in newborn mice (5,13). Thus, the strain SR-11 seemed to have high virulence and, therefore, may provide a useful system for comparing the virulence of hantaviruses in mice.…”

“…Tamura et al reported that two virus clones of Hantaan virus, c1-1 and c1-2, indicated the manifest divergence in virulence in newborn mice, although there is no difference between both clones in viral replication in culture cells or peritoneal exudate cells (13). They suggested that the suppression of host immunity by c1-1, not humoral but T-cell mediated immunity, caused the difference of virulence between the two clones.…”