Experimental parameters of infection and intraspecific transmission of Hantaan virus, the etiologic agent of Korean hemorrhagic fever, in Apodemus agrarius rodents were determined. Mice inoculated by the intramuscular route experienced viremia for about 1 week beginning on day 7. After 3 weeks, immunofluorescent and neutralizing antibodies were present and no mouse ever developed signs of acute illness. Virus was recovered from lung, kidney, salivary gland, and liver, and virus excretion in urine, saliva, and feces occurred from about day 10 through day 360 (urine) post-inoculation. Antigen, but not infectious virus, was persistent in lung tissue for as long as 1 year. Horizontal contact infection occurred among cage-mates regardless of sexual pairing up to 360 days after infection and no evidence for participation of ectoparasitic arthropods in such transmission was obtained.
To determine the extent of hantavirus infection in Singapore, serological studies using the indirect immunofluorescent antibody (IFA) test were conducted on commensal rodents and on human patients in 4 diagnostic groups. Virus isolation using a Vero E6 cell line was performed on hantaviral antigen-positive rodent lung tissue. Of 142 rodents and 3 insectivores studied, 37 (26%) were seropositive for IFA. Rattus norvegicus was the predominant species captured, with the highest species-specific seropositive rate of 32% (36 of 113). A hantavirus strain, R36, was isolated from one R. norvegicus. Seropositive rates for human patients were: 8% respectively for dengue haemorrhagic fever suspects and for non-A non-B hepatitis patients, 3% for leptospirosis suspects and 2% for acute nephritis patients. 2 patients had marked liver dysfunction but mild renal involvement. This hepatitis-like manifestation appears to be a clinical variant of hantavirus infection.
SUMMARYViruses isolated from the blood of two Korean haemorrhagic fever patients were propagated in cell culture and compared to prototype Hantaan virus which was isolated from Apodemus mice. The antigenic properties of the human isolates were found to be closely related to Hantaan virus by plaque reduction neutralization, haemagglutination inhibition and fluorescent antibody staining with both polyclonal and monoclonal antibodies. The medium genome segment of each human isolate was sequenced and compared to that of Hantaan virus. Nucleotides comprising the Hantaan virus G 1 and G2 envelope protein-coding regions differed from those of the other viruses by only 5.4~o and 5-7~o. The human isolates differed from one another by 1.6~. The nucleotide differences resulted in predicted amino acid variations of 1.3~ to 2-3~ among the three viruses, with the majority occurring as conservative substitutions in G1.
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