Sex differences in the recognition of and innate antiviral responses to Seoul virus in Norway rats.

Among rodents that carry hantaviruses, more males are infected than females. Male rats also have elevated copies of Seoul virus RNA and reduced transcription of immune-related genes in the lungs than females. To further characterize sex differences in antiviral defenses and whether these differences are mediated by gonadal hormones, we examined viral RNA in the lungs, virus shedding in saliva, and antiviral defenses among male and female rats that were intact, gonadectomized neonatally, or gonadectomized in adulthood. Following inoculation with Seoul virus, high amounts viral RNA persisted longer in lungs from intact males than intact females. Removal of the gonads in males reduced the amount of viral RNA to levels comparable with intact females at 40 days post-inoculation (p.i.). Intact males shed more virus in saliva than intact females 15 days p.i.; removal of the gonads during either the neonatal period or in adulthood increased virus shedding in females and decreased virus shedding in males. Induction of pattern recognition receptors (PRRs; Tlr7 and Rig-I), expression of antiviral genes (Myd88, Visa, Jun, Irf7, Ifnbeta, Ifnar1, Jak2, Stat3, and Mx2), and production of Mx protein was elevated in the lungs of intact females compared with intact males. Gonadectomy had more robust effects on the induction of PRRs than on downstream IFNbeta or Mx2 expression. Putative androgen and estrogen response elements are present in the promoters of several of these antiviral genes, suggesting the propensity for sex steroids to directly affect dimorphic antiviral responses against Seoul virus infection.

Persistent Seoul virus infection in Lewis rats.

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.

[Passage adaptability of candidate strains for hemorrhagic fever with renal syndrome purified vaccine in Vero cells and their immunogenicity].

OBJECTIVE: To adapt the candidate strains of hemorrhagic fever with renal syndrome (HFRS) purified vaccine to Vero cells and to study their antigenicity and immunogenicity. METHODS: The viral strains H8207 (Hantaan virus, HTN) and Y86013 (Seoul virus, SEO) were continuously propagated in Vero cell by the terminal dilution method and studied the characteristics of virus multiplication, viral titers and the amounts of virus antigen after serial passages. Three batches of crude monovalent inactivated vaccine were developed using the different passages of these 2 viral strains. RESULTS: The strains H8207 and Y86013 adapted to Vero cells and stably grew on the cells with high titers. Rabbits immunized with the crude vaccines of H8207 and Y86013 showed 100% sero-conversion and the neutralizing antibody titers of the rabbit immune sera reached 1?10 at 4 weeks after 2 times of immunization. CONCLUSIONS: The results suggest that these 2 candidate strains had adapted to Vero cells, possessed high titers and good immunogenicity and be feasible to prepare the HFRS purified vaccine in Vero cells.