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Ex Vivo Infection of Human Lymphoid Tissue and Female Genital Mucosa with Human Immunodeficiency Virus 1 and Histoculture
Published on: October 12, 2018
HIV infection en route to endogenization: two cases
P Colson1, I Ravaux, C Tamalet
1Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), UM63 CNRS 7278 IRD 198 INSERM U1095, Aix-Marseille Université, Marseille, France; Fondation Institut Hospitalo-Universitaire (IHU) MéiterranéInfection, 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.
Human immunodeficiency virus (HIV) may naturally integrate into the human genome, potentially leading to a functional cure. This process, known as endogenization, offers a new perspective beyond viral eradication.
Area of Science:
- Virology
- Human Genetics
- Immunology
Background:
- The long-term evolution of human immunodeficiency virus (HIV) and its integration into the human genome is not fully understood.
- Many vertebrates harbor endogenous retroviruses, prompting investigation into possible HIV endogenization.
Observation:
- Two HIV-infected patients with no detectable viremia or disease were studied.
- HIV DNA integrated into the host genome was sequenced using Sanger and deep sequencing.
- Viral sequences showed high rates of inactivating mutations, specifically tryptophan codon to stop codon transformations.
Findings:
- Integrated HIV DNA in both patients was largely inactivated due to widespread stop codon mutations.
- Strong immune responses were observed in one patient, suggesting a past productive infection.
- The APOBEC enzyme, which targets viral RNA, may have been activated early and effectively, aided by the lack of Vif inhibition.
Implications:
- HIV endogenization, similar to other endogenous retroviruses, is proposed as a potential natural cure for HIV.
- This contrasts with the goal of complete viral eradication, suggesting a paradigm shift in HIV cure strategies.
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