Evidence for Limited Genetic Compartmentalization of HIV-1 between Lung and Blood

Abstract

BackgroundHIV-1 is frequently detected in the lungs of infected individuals and is likely important in the development of pulmonary opportunistic infections. The unique environment of the lung, rich in alveolar macrophages and with specialized local immune responses, may contribute to differential evolution or selection of HIV-1.Methodology and FindingsWe characterized HIV-1 in the lung in relation to contemporaneous viral populations in the blood. The C2-V5 region of HIV-1 env was sequenced from paired lung (induced sputum or bronchoalveolar lavage) and blood (plasma RNA and proviral DNA from sorted or unsorted PBMC) from 18 subjects. Compartmentalization between tissue pairs was assessed using 5 established tree or distance-based methods, including permutation tests to determine statistical significance. We found statistical evidence of compartmentalization between lung and blood in 10/18 subjects, although lung and blood sequences were intermingled on phylogenetic trees in all subjects. The subject showing the greatest compartmentalization contained many nearly identical sequences in BAL sample, suggesting clonal expansion may contribute to reduced viral diversity in the lung in some cases. However, HIV-1 sequences in lung were not more homogeneous overall, nor were we able to find a lung-specific genotype associated with macrophage tropism in V3. In all four subjects in whom predicted X4 genotypes were found in blood, predicted X4 genotypes were also found in lung.ConclusionsOur results support a picture of continuous migration of HIV-1 between circulating blood and lung tissue, with perhaps a very limited degree of localized evolution or clonal replication.

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“…[10][11][12][13][14] Whether the same is true within TB coinfected granulomas is currently unclear and inconclusive. [15][16][17] Understanding the dynamics of viral evolution within this unique highly compartmentalized but immunologically active environment is important to virus eradication strategies. The nature of the viral variants, their response to treatment, and the mechanisms that govern their progression to sequestration may play critical roles in clinical patient management.…”

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The role of HIV integration in viral persistence: no more whistling past the proviral graveyard

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