Abstract
To characterize the occurrence, frequency, and kinetics of retroviral recombination in vivo, we intravaginally inoculated rhesus macaques, either simultaneously or sequentially, with attenuated simian immunodeficiency virus (SIV) strains having complementary deletions in their accessory genes and various degrees of replication impairment. In monkeys inoculated simultaneously with SIVmac239Δ
vpx/
Δ
vpr
and SIVmac239Δ
nef
, recombinant wild-type (wt) virus and wild-type levels of plasma viral RNA (vRNA) were detected in blood by 2 weeks postinoculation. In monkeys inoculated first with SIVmac239Δ
vpx/
Δ
vpr
and then with SIVmac239Δ
nef
, recombination occurred but was associated with lower plasma vRNA levels than plasma vRNA levels seen for monkeys inoculated intravaginally with wt SIVmac239. In one monkey, recombination occurred 6 weeks after the challenge with SIVmac239Δ
nef
when plasma SIVmac239Δ
vpx/
Δ
vpr
RNA levels were undetectable. In monkeys inoculated first with the more highly replicating strain, SIVmac239Δ
nef
, and then with SIVmac239Δ
vpx/
Δ
vpr
, wild-type recombinant virus was not detected in blood or tissues. Instead, a virus that had repaired the deletion in the
nef
gene by a compensatory mutation was found in one animal. Overall, recombinant SIV was eventually found in four of six animals intravaginally inoculated with the two SIVmac239 deletion mutants. These findings show that recombination can occur readily in vivo after mucosal SIV exposure and thus contributes to the generation of viral genetic diversity and enhancement of viral fitness.
