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Population dynamics of the viral quasipecies during SIV infection: association of early sequence selection with the rate of progression to AIDS.
Amedee AM; Lacour N; Bakeer M; Simpson L; Martin L; Bohm R; Murphey-Corb
January 30, 1997
Int Conf AIDS. 1996 Jul 7-12;11(2):5 (abstract no. We.A.141). Unique

Objective: To determine whether the dramatic differences in survival observed in macaques infected with SIV is linked to selective infection of genotypes found within the viral quasispecies. Methods: The proviral content of peripheral blood mononuclear cells during the course of infection in animals undergoing variable rates of disease progression was genetically analyzed by sequence analysis and heteroduplex mobility shift assays of PCR products specific for the first hypervariable region of the viral gp120. Monkeys were inoculated with SIV/17E-Fr, a minimally immunopathogenic molecular clone, and/or the primary virulent isolate SIV/DeltaB670. Results: Complex mixtures of genotypes were identified in rapid progressors during primary infection that persisted until death. Infection of slow progressors on the other hand was characterized by dominance of a single genotype early in infection that was maintained during clinical latency. Signs of disease that occurred late in slow progressors was associated with the emergence of genetic variants that had diverged from the dominant genotype. Although 16 distinct genotypes from the inoculum were identified among rapid progressors, two genotypes dominated infection of slow progressors: SIV/17E-Fr, which is minimally pathogenic, and SIV/DeltaB670-Cl 3, a genotype selectively amplified by chronic in vitro culture. Conclusions: These data suggest that factors that dictate the rate of disease progression are active during the initial rounds of virus replication and appear to be targeted primarily to viral genotypes undergoing the most rapid replication.

*Simian Acquired Immunodeficiency Syndrome/VIROLOGY *SIV/GENETICS *Virus Replication