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ONGOING HIV-1 EVOLUTION AND RESERVOIR RESEEDING IN TWO ELITE CONTROLLERS WITH GENETICALLY DIVERSE PERIPHERAL PROVIRAL QUASISPECIES
Reservatório proviral
Diversidade viral
Evolução viral
Controladores de elite
Author
Affilliation
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de AIDS & Imunologia Molecular. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de AIDS & Imunologia Molecular. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de AIDS & Imunologia Molecular. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de AIDS & Imunologia Molecular. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de AIDS & Imunologia Molecular. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de AIDS & Imunologia Molecular. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de AIDS & Imunologia Molecular. Rio de Janeiro, RJ, Brasil.
Abstract
BACKGROUND Elite controllers (EC) are human immunodeficiency virus (HIV)-positive individuals who can maintain low viral
loads for extended periods without antiretroviral therapy due to multifactorial and individual characteristics. Most have a small
HIV-1 reservoir composed of identical proviral sequences maintained by clonal expansion of infected CD4+ T cells. However,
some have a more diverse peripheral blood mononuclear cell (PBMC)-associated HIV-1 reservoir with unique sequences.
OBJECTIVES To understand the turnover dynamics of the PBMC-associated viral quasispecies in ECs with relatively diverse
circulating proviral reservoirs.
METHODS We performed single genome amplification of the env gene at three time points during six years in two EC with high
intra-host HIV DNA diversity.
FINDINGS Both EC displayed quite diverse PBMCs-associated viral quasispecies (mean env diversity = 1.9-4.1%) across all timepoints
comprising both identical proviruses that are probably clonally expanded and unique proviruses with evidence of ongoing
evolution. HIV-1 env glycosylation pattern suggests that ancestral and evolving proviruses may display different phenotypes of
resistance to broadly neutralising antibodies consistent with persistent immune pressure. Evolving viruses may progressively
replace the ancestral ones or may remain as minor variants in the circulating proviral population.
MAIN CONCLUSIONS These findings support that the high intra-host HIV-1 diversity of some EC resulted from long-term
persistence of archival proviruses combined with the continuous reservoir’s reseeding and low, but measurable, viral evolution
despite undetectable viremia.
Keywords in Portuguese
HIV-1Reservatório proviral
Diversidade viral
Evolução viral
Controladores de elite
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