HIV infection en route to endogenization: two cases

November 15, 2014 at 9:40 am

Clinical Microbiology and Infection

Philippe Colson1,2, Isabelle Ravaux3, Catherine Tamalet1,2, Olga Glazunova2, Emeline Baptiste1, Eric Chabriere1, Aurélie Wiedemann4,5, Christine Lacabaratz4,5, Mohamed Chefrour6, Christophe Picard7, Andreas Stein2,3, Yves Levy4,5,8 andDidier Raoult1,2,*

1Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), UM63 CNRS 7278 IRD 198 INSERM U1095, Aix-Marseille Univ, Marseille, France

2Fondation Institut Hospitalo-Universitaire (IHU) Méditerranée Infection, Pôle des Maladies Infectieuses et Tropicales Clinique et Biologique, Fédération de Bactériologie-Hygiène-Virologie, Centre Hospitalo-Universitaire Timone, Assistance Publique-Hôpitaux de Marseille, Marseille, France

3IHU Méditerranée Infection, Pôle des Maladies Infectieuses et Tropicales Clinique et Biologique, Service des Maladies Infectieuses, hôpital Conception, Marseille, France

4Université Paris Est, Faculté de médecine, Créteil, France

5Vaccine Research Institute (VRI), Créteil, France

6Laboratoire de Biochimie, Centre Hospitalo-Universitaire Timone, Assistance Publique-Hôpitaux de Marseille, Marseille, France

7Aix-Marseille Université, CNRS, EFS, ADES UMR 7268, Marseille, France

8AP-HP, Hôpital H. Mondor – A. Chenevier, Service d’immunologie clinique et maladies infectieuses, Créteil, France

*Corresponding author: Prof. Didier RAOULT, IHU Méditerranée Infection, URMITE, Unité des Rickettsies, Faculté de Médecine, Aix-Marseille Université, 27 boulevard Jean Moulin, 13385 Marseille cedex 05, France. Tel. +33 491 32 43 75; email: didier.raoult@gmail.com

The long-term spontaneous evolution between humans and the human immunodeficiency virus (HIV) is not well characterized; many species, including humans, exhibit remnants of other retroviruses in their genomes that question such possible endogenization of HIV.

We investigated two HIV-infected patients with no HIV-related disease and no detection with routine tests of plasma HIV RNA or cell-associated HIV DNA. We used Sanger and deep sequencing to retrieve HIV DNA sequences integrated in the human genome and tested the host humoral and cellular immune responses.

We noticed that viruses from both patients were inactivated by the high prevalence of the transformation of tryptophan codons into stop codons (25% overall (3-100% per gene) and 24% overall (0-50% per gene)).

In contrast, the humoral and/or cellular responses were strong for one patient and moderate for the other, indicating that a productive infection occurred at one stage of the infection.

We speculate that the stimulation of APOBEC, the enzyme group that exchanges G for A in viral nucleic acids and is usually inhibited by the HIV protein Vif, has been amplified and made effective from the initial stage of the infection.

Furthermore, we propose that HIV cure may occur through HIV endogenization in humans, as observed for many other retroviruses in mammals, rather than clearance of all traces of HIV from human cells which defines viral eradication.

PDF

http://onlinelibrary.wiley.com/doi/10.1111/1469-0691.12807/pdf

Entry filed under: Biología Molecular, HIV/SIDA, HIV/SIDA Laboratorio, Metodos diagnosticos. Tags: .

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