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CD81 association with SAMHD1 enhances HIV-1 reverse transcription by increasing dNTP levels

2017; Nature Portfolio; Volume: 2; Issue: 11 Linguagem: Inglês

10.1038/s41564-017-0019-0

2058-5276

Vera Rocha‐Perugini, Henar Suárez, Susana Álvarez, Soraya López‐Martín, Gina M. Lenzi, Felipe Vences‐Catalán, Shoshana Levy, Baek Kim, María Ángeles Muñoz‐Fernández, Francisco Sánchez‐Madrid, Marı́a Yáñez-Mó,

Cell Adhesion Molecules Research

In this study, we report that the tetraspanin CD81 enhances human immunodeficiency virus (HIV)-1 reverse transcription in HIV-1-infected cells. This is enabled by the direct interaction of CD81 with the deoxynucleoside triphosphate phosphohydrolase SAMHD1. This interaction prevents endosomal accumulation and favours the proteasome-dependent degradation of SAMHD1. Consequently, CD81 depletion results in SAMHD1 increased expression, decreasing the availability of deoxynucleoside triphosphates (dNTP) and thus HIV-1 reverse transcription. Conversely, CD81 overexpression, but not the expression of a CD81 carboxy (C)-terminal deletion mutant, increases cellular dNTP content and HIV-1 reverse transcription. Our results demonstrate that the interaction of CD81 with SAMHD1 controls the metabolic rate of HIV-1 replication by tuning the availability of building blocks for reverse transcription, namely dNTPs. Together with its role in HIV-1 entry and budding into host cells, the data herein indicate that HIV-1 uses CD81 as a rheostat that controls different stages of the infection. CD81 is shown to interact with SAMHD1 and lead to its proteasomal degradation, thereby impacting dNTP availability and enhancing HIV-1 reverse transcription in primary human T cells.