Pathogenesis of Rift Valley fever virus (RVFV) in inbred rats.
The pathogenesis of Rift Valley fever in adult rats from 3 inbred strains (LEW, MAXX, WF) was investigated. WF rats all died by day 2 postinoculation with viral tissue titers reaching 9 log10 PFU/g. LEW and MAXX rats were resistant to liver disease, but fatal necrotising encephalitis developed in 16 and 44% of the rats, respectively. Detection of serum neutralising antibody on day 3 coincided with clearance of virus from serum and liver, although infectious virus was detected in spleen homogenates as late as day 19 postinfection. Viral titers in LEW and MAXX rats did not exceed 4.5 log10 PFU/g. Cyclophosphamide immunosuppression of LEW rats led to death 5-9 days postinfection; early patterns of viral replication were not affected, but continued growth in the liver resulted in fatal hepatitis. These animals could be protected by passive antibody therapy administered on days 2-5 postinfection to mimic the serum neutralising antibody pattern seen in unmanipulated infected LEW rats. Thus, RVF virus replication and spread is rapid in the WF rats tissues, whereas in LEW and MAXX rats viral growth is less due to an intrinsic mechanism which allows sufficient time for an immune response to terminate infection. A slightly diminished immune response may lead to the development of encephalitis more frequently in MAXX than LEW rats. These rat strains should be useful in elucidating those mechanisms of resistance which limit RVFV-induced hepatitis and encephalitis.
D000818:Animals; D000956:Antigens, Viral / Q000032:analysis; D003520:Cyclophosphamide / Q000494:pharmacology; D004261:DNA Replication; D004195:Disease Models, Animal; D007165:Immunosuppression Therapy; D007700:Kinetics; D051381:Rats; D011917:Rats, Inbred Lew; D011919:Rats, Inbred Strains; D011920:Rats, Inbred WF; D012295:Rift Valley Fever / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D012296:Rift Valley fever virus / Q000235:genetics / Q000302:isolation & purification; D014779:Virus Replication
D000956:Antigens, Viral; D003520:Cyclophosphamide