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bioRxiv · 10.1101/2021.08.29.458043

HIV-1 Mutants that Escape the Cytotoxic T-Lymphocytes are Defective in Viral DNA Integration

Balasubramaniam, M.·Thapa, S.·Davids, B.-O.·Bryer, A.·Xu, C.·Shi, J.·Aiken, C.·Pandhare, J.·Perilla, J. R.·Dash, C.
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Abstract

ABSTRACT HIV-1 replication is durably controlled in certain untreated HIV-1-infected individuals expressing particular human leukocyte antigens (HLA). These HLAs tag infected cells for elimination by presenting specific viral epitopes to CD8+ cytotoxic T-lymphocytes (CTL). In individuals expressing HLA-B27, CTLs primarily target the capsid protein (CA)-derived KK10 epitope. Selection of CA mutation R264K helps HIV-1 escape the CTL response but severely diminishes virus infectivity. Here we report that the R264K mutation-associated infectivity defect arises primarily from impaired viral DNA integration. Strikingly, selection of the compensatory CA mutation S173A or depletion of host cyclophilin A largely rescues the R264K-associated integration and infectivity defects. Collectively, our study reveals novel mechanistic insights into the fitness defect incurred by an HIV-1 variant escaping a CA-directed CTL response.

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Balasubramaniam, M., Thapa, S., Davids, B.-O., Bryer, A., Xu, C., Shi, J., Aiken, C., Pandhare, J., Perilla, J. R., Dash, C.. 2021-08-29. HIV-1 Mutants that Escape the Cytotoxic T-Lymphocytes are Defective in Viral DNA Integration. https://doi.org/10.1101/2021.08.29.458043

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