Attenuation phenotype of a cell culture-adapted variant of hepatitis A virus (HM175/p16) in susceptible New World owl monkeys.
The virulence of a clonally isolated, cell culture-adapted hepatitis A virus (HM175/p16) was assessed in 4 seronegative owl monkeys inoculated intravenously with 2.8 x 10(4) radioimmunofocus-forming units of virus. The virus was highly attenuated, even though its complete nucleotide sequence contains only 19 mutations from the wild-type genome. Only 3 monkeys developed antibodies to hepatitis A virus (only 2 within 96 days of virus inoculation). One monkey had viremia and significantly elevated serum aminotransferase levels. In this animal, maximum viremia and fecal shedding of virus occurred 30-33 days after inoculation. In contrast, in earlier studies of a related cell culture-adapted but still hepatovirulent virus (HM175/S18), viremia was documented in 6 of 6 animals and peak viremia and fecal shedding of virus occurred 18 or 19 days after intravenous inoculation of about one-tenth as much virus.
Taylor
K L
KL
United States Army Medical Research Institute for Infectious Diseases, Fort Detrick, Frederick, Maryland.
Murphy
P C
PC
Asher
L V
LV
LeDuc
J W
JW
Lemon
S M
SM
D000220:Adaptation, Biological; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000917:Antibody Formation; D016645:Aotidae; D004198:Disease Susceptibility; D005260:Female; D014644:Genetic Variation; D006506:Hepatitis A / Q000235:genetics / Q000276:immunology / Q000662:veterinary*; D006507:Hepatovirus / Q000254:growth & development / Q000302:isolation & purification / Q000472:pathogenicity*; D008099:Liver / Q000473:pathology / Q000648:ultrastructure; D008297:Male; D009154:Mutation; D010641:Phenotype; D012692:Serial Passage; D013156:Splenectomy; D013997:Time Factors; D014766:Viremia; D014774:Virulence; D017201:Virus Shedding; D005723:gamma-Glutamyltransferase / Q000097:blood
D005723:gamma-Glutamyltransferase; D000410:Alanine Transaminase