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J Acquir Immune Defic Syndr. 2011 Feb 1;56(2):100-8. doi: 10.1097/QAI.0b013e3181fe9450.

Reduced replication capacity of NL4-3 recombinant viruses encoding reverse transcriptase-integrase sequences from HIV-1 elite controllers.

Author information

1
Faculty of Health Sciences, Simon Fraser University, Burnaby, BC, Canada.

Abstract

BACKGROUND:

Identifying viral and host determinants of HIV-1 elite control may help inform novel therapeutic and/or vaccination strategies. Previously, we observed decreased replication capacity in controller-derived viruses suggesting that fitness consequences of human leukocyte antigen (HLA) class I-associated escape mutations in Gag may contribute to this phenotype. This study examines whether similar functional defects occur in Pol proteins of elite controllers.

METHODS:

Recombinant NL4-3 viruses encoding plasma RNA-derived reverse transcriptase-integrase sequences from 58 elite controllers and 50 untreated chronic progressors were constructed, and replication capacity measured in vitro using a green fluorescent protein (GFP) reporter T-cell assay. Sequences were analyzed for drug resistance and HLA-associated viral polymorphisms.

RESULTS:

Controller-derived viruses displayed significantly lower replication capacity compared with those from progressors (P < 0.0001). Among controllers, the most attenuated viruses were generated from individuals expressing HLA-B*57 or B*51. In viruses from B*57+ progressors (n = 8), a significant inverse correlation was observed between B*57-associated reverse transcriptase-integrase escape mutations and replication capacity (R = -0.89; P = 0.003); a similar trend was observed in B*57+ controller-derived viruses (n = 20, R = -0.36; P = 0.08).

CONCLUSIONS:

HIV-1 Pol function seemed to be compromised in elite controllers. As observed previously for Gag, HLA-associated immune pressure in Pol may contribute to viral attenuation and subsequent control of viremia.

PMID:
21124229
PMCID:
PMC3078702
DOI:
10.1097/QAI.0b013e3181fe9450
[Indexed for MEDLINE]
Free PMC Article

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