Abstract
BackgroundOngoing intra-host HIV-1 evolution has been shown in individuals that naturally suppress the viremia to low levels (HIV controllers) by the analysis of the RNA in plasma compartment. Detection of evolution at the DNA proviral compartment in HIV controllers, however, has been more challenging and the precise correlation between the systemic viral suppression level and rate of reservoir’s reseeding in those individuals is not fully understood. In this sense, we examined the proviral DNA quasispecies by single genome amplification of the env gene in a cohort of 23 HIV controllers from Brazil, divided in three groups, according to the level of systemic viral suppression: (1) elite controllers with persistent undetectable viral load (PEC, n = 6); (2) elite controllers with occasional episodes of transient (51–400 copies/mL) viremia (EEC, n = 7); and (3) viremic controllers with persistent low-level (80–2000 copies/mL) viremia (VC, n = 10).ResultsThe HIV-1 diversity of the PBMC-associated proviral quasispecies in EC was significantly (P < 0.01) lower than in VC, but not significantly different between PEC and EEC groups. We detected a considerable variation in the average pairwise nucleotide distance and proportion of unique sequences in the HIV-1 proviral quasispecies of PEC and EEC. Some PEC and EEC displayed highly homogenous proviral populations with large clusters of identical sequences, while others exhibited relatively diverse proviral populations with a high proportion of unique sequences comparable to VC subjects. The long-term (10–15 years) follow-up of the HIV-1 proviral populations revealed a complete evolutionary stasis in one PEC and measurable divergence rates in one EEC [3.1 (1.2–5.6) × 10−3 substitutions/site/year and one VC [2.9 (0.7–5.1) × 10−3 substitutions/site/year].ConclusionsThere is no simple relationship between systemic viral suppression and intra-host proviral diversity or rate of reservoir’s reseeding in chronically infected HIV controllers. Our results demonstrate that very divergent patterns of intra-host viral diversity and divergence could be detected in the setting of natural suppression of HIV-1 replication and that ongoing evolution and reseeding of the PBMC proviral reservoir occurs in some elite controllers.
Highlights
Ongoing intra-host human immunodeficiency virus type-1 (HIV-1) evolution has been shown in individuals that naturally suppress the viremia to low levels (HIV controllers) by the analysis of the RNA in plasma compartment
Our results demonstrate that very divergent patterns of intra-host viral diversity and divergence could be detected in the setting of natural suppression of HIV-1 replication and that ongoing evolution and reseeding of the peripheral blood mononuclear cells (PBMC) proviral reservoir occurs in some elite controllers
A previous study conducted by our group demonstrated that rare episodes of detectable viremia in elite controllers (EC) are associated to higher levels of systemic immune activation and a stronger HIV-1 specific immune response [21], pointing to lower levels of systemic viral supression in elite controllers (EEC) than in persistent elite controllers (PEC), we found no significant difference in the quasispecies diversity between both EC subgroups
Summary
Ongoing intra-host HIV-1 evolution has been shown in individuals that naturally suppress the viremia to low levels (HIV controllers) by the analysis of the RNA in plasma compartment. Detection of evolution at the DNA proviral compartment in HIV controllers, has been more challenging and the precise correlation between the systemic viral suppression level and rate of reservoir’s reseeding in those individuals is not fully understood. Intra-host HIV-1 evolution in TP follows a consistent pattern of temporal changes in viral diversity and divergence during the course of infection, that affect both proviral DNA populations in peripheral blood mononuclear cells (PBMC) and viral RNA populations in plasma [3]. In some LTNPs, DNA proviral populations are composed of a complex mixture of archival (dating close to the patient’s seroconversion time) and recent (dating close to the sampling time) variants [13] and displayed no temporal structure in the changes of diversity and divergence during chronic infection [14]. A recent study demonstrates that most proviral sequences detected in PBMC from HIV controllers are largely representative of archival variants probably integrated during primary infection and propagated by clonal expansion of the memory CD4+ T cell latent reservoir, rare proviral clones of recent origin could be detected in some patients [12]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
