2. Academic Validation
  3. CD81 association with SAMHD1 enhances HIV-1 reverse transcription by increasing dNTP levels

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

  • Nat Microbiol. 2017 Nov;2(11):1513-1522. doi: 10.1038/s41564-017-0019-0.
Vera Rocha-Perugini 1 2,  Henar Suárez 3,  Susana Álvarez 4,  Soraya López-Martín 3,  Gina M Lenzi 5,  Felipe Vences-Catalán 6,  Shoshana Levy 6,  Baek Kim 5,  María A Muñoz-Fernández 4,  Francisco Sánchez-Madrid 1 2 7,  Maria Yáñez-Mó 8
Affiliations

Affiliations

  • 1 Servicio de Inmunología, Hospital de la Princesa, Instituto de Investigación Sanitaria La Princesa (IIS-IP), Madrid, 28006, Spain.
  • 2 Vascular Pathophysiology Research Area, Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, 28029, Spain.
  • 3 Departamento de Biología Molecular, Universidad Autónoma de Madrid, Instituto de Investigación Sanitaria La Princesa (IIS-IP), Centro de Biología Molecular Severo Ochoa, Madrid, 28049, Spain.
  • 4 Servicio de Inmunobiología Molecular del Hospital Universitario Gregorio Marañón, Madrid, 28007, Spain.
  • 5 Center for Drug Discovery, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, 30332, USA.
  • 6 Division of Oncology, Center for Clinical Sciences Research, Stanford University, Stanford, CA, 94305-5151, USA.
  • 7 CIBER Cardiovascular, Madrid, Spain.
  • 8 Departamento de Biología Molecular, Universidad Autónoma de Madrid, Instituto de Investigación Sanitaria La Princesa (IIS-IP), Centro de Biología Molecular Severo Ochoa, Madrid, 28049, Spain. [email protected].
PMID: 28871089 DOI: 10.1038/s41564-017-0019-0
Abstract

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.

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