There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.
Abstract
Background
Many infected subjects acquire 2 or more strains of HIV-1, in some cases both CTL
escape-mutants (EM) and wild-type (WT) variants. Eventual reversion to WT reflects
fitter WT virus in vivo. However, reported reversion rates vary widely. Understanding
reversion (and how to maintain unfit EM variants) should facilitate better approaches
to HIV-1 control. We hypothesised that co-transmission of WT virus in the infecting
inoculum leads to rapid reversion and more pathogenic infections.
Methods
A quantitative RT-PCR simultaneously measures WT and EM viral loads at the Mane-A*10-restricted
SIV Gag KP9164-172 CTL epitope in pigtail macaques. Reversion of the K165R EM viruses
from 5 SIV and SHIV inocula were assessed in 15 naïve A*10-ve macaques.
Results
Infection with isolates containing ≥10% WT SIVmac239, SHIVmn229 or SHIVSF162P3 all
show rapid growth of both WT and EM virus during acute infection and EM virus decays
rapidly thereafter. Conversely, delayed reversion occurs in animals infected with
a SIVmac239 K165R clone, and ≤4% WT SHIVs. Further, the reversion rate is proportional
to target CD4 T cell number. Importantly, EM inocula with delayed reversion are less
pathogenic, showing reduced peak and set point viral load compared to those infected
with ≥10% WT in the inocula and showing rapid reversion (P = 0.0094, P = 0.0072 respectively).
Conclusion
When infected with 2 viruses (both EM and >10%WT), rapid outgrowth of WT virus occurs
during acute infection. Delayed reversion to WT results if only EM virus initiates
the infection, primarily due to some target cell depletion by the EM virus during
acute infection prior to the appearance of WT virus. The delay in reversion, where
acute viremia is primarily the less fit EM virus, results in a significant reduction
in VL and will delay disease. This has implications for vaccine strategies to maintain
weaker EM viruses in new hosts.