Characterization of Less Pathogenic Infectious Molecular Clones Derived from Acute-Pathogenic SHIV-89.6P Stock Virus

Abstract

For a better understanding of the acute pathogenicity of SHIV-89.6P stock virus, which induces prominent CD4 cell loss within a month after inoculation in monkeys, we have constructed four infectious molecular clones (cl 18, cl 64, cl 69, and cl 71). Cl 64, cl 69, and cl 71, like the parental virus, showed a high in vitro replication ability and a pathogenic-like effect (CD4 downmodulation) in a monkey CD4+ cell line, whereas cl 18 showed a lower replication ability and could not downmodulate CD4. Cl 64, which has characteristics similar to those of the parental virus in vitro, was inoculated into four rhesus monkeys. All monkeys showed a plasma viral load similar to that of the parental virus with a peak at 2 weeks after inoculation. However, the viral load gradually decreased and the virus failed to cause an AIDS-like disease in infected monkeys, but it induced a strong antiviral antibody response. These results demonstrate the polyclonal nature of the parental SHIV-89.6P virus stock and demonstrate that cl 64, aside from its high replicability, may differ qualitatively from the parental virus.