Persistent Infection of Rats with Haemorrhagic Fever with Renal Syndrome Virus and their Antibody Responses

Abstract

SUMMARYNewborn (within 24 h after birth), 1-week-old and 6-week-old (adult) rats were inoculated with a Hantaan-related virus (B-l) and attempts were made to isolate the virus from various organs. Virus-specific antigens were detected in various organs of newborn rats. Moreover virus could be isolated from almost all their organs even 25 weeks after infection. In contrast, in rats infected at 6 weeks of age the virus could be isolated from various organs but its concentration decreased progressively with time. The levels of haemagglutination-inhibiting (HI) and neutralizing antibodies to B-1 Virus in the sera were measured. In adult rats, HI antibodies were first detected 2 weeks after infection and their titre rose to a maximum after 5 weeks. On the other hand, in newborn rats the levels of antibodies remained low until 5 or 6 weeks after infection and started to increase to a high level more than 9 weeks after infection. Furthermore, in rats infected soon after birth IgM antibodies predominated for a long time and these antibodies also neutralized infectivity at a high level. These data suggest that the induction of a high titre of neutralizing antibodies mainly of the IgM type does not result in virus clearance in newborn rats and that cellular immunity may be important for virus clearance in vivo.

Persistent hantavirus infections: characteristics and mechanisms

“…or i.p. infection with Hantaan or Seoul viruses 10,[13][14][15][16][17] . In nature, it is likely that infection of newborn rodents only occurs by aerosol exposure or contact with a recently infected dam; the significance of these findings is therefore unclear.…”

“…As was found for Hantaan virus infection of Apodemus, experimentally inoculated and wild-caught Seoul-virus-infected rats excrete virus in urine; however, virus shedding is not consistently observed 20 . Although both naturally and experimentally infected rats have viral antigen in many of their tissues and organs, with lungs generally having the highest antigen concentration 13,20 , the duration of Seoul virus persistence is poorly defined. In separate studies, newborn rats were found to have viral antigen in their organs for at least 25 weeks 13 and adult rats for at least 75 days 20 after infection ( Table 2).…”

“…Although both naturally and experimentally infected rats have viral antigen in many of their tissues and organs, with lungs generally having the highest antigen concentration 13,20 , the duration of Seoul virus persistence is poorly defined. In separate studies, newborn rats were found to have viral antigen in their organs for at least 25 weeks 13 and adult rats for at least 75 days 20 after infection ( Table 2). This age-dependent difference in Seoul virus persistence in rats has also been observed in two other studies.…”

“…38). This mechanism probably does not apply to hantaviruses, which replicate in many tissues and organs that are readily accessed by the host immune system, resulting in vigorous humoral responses 3,13,21,39 . Little is known about the hosts' cell-mediated immune responses during hantaviral persistence.…”

Role of T Lymphocyte Subsets in Protection and Recovery from Hantaan Virus Infection in Mice

“…Infection of newborn rodents with hantaviruses was fatal (Tsai et al, 1982;Kurata et al, 1983;Yamanouchi et al, 1984;Kim et al, 1985;Tanishita et al, 1986), but infection of adults with these viruses resulted in prolonged infection without any clinical symptoms Yanagihara et al, 1985a, b). Recently, T cellmediated immunity was suggested to play a crucial role in resistance of mice to HV infection (Nakamura et al, 1985 a, b).…”