HIV infection en route to endogenization: two cases

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HIV infection en route to endogenization: two cases P. Colson, I. Ravaux, C. Tamalet, O. Glazunova, E. Baptiste, E. Chabriere, A. Wiedemann, C. Lacabaratz, M. Chefrour, C. Picard, A. Stein, Y. Levy, D. Raoult Clinical Microbiology and Infection Volume 20, Issue 12, Pages 1280-1288 (December 2014) DOI: 10.1111/1469-0691.12807 Copyright © 2014 European Society of Clinical Infectious Diseases Terms and Conditions

FIG. 1 (a) Western blot HIV-1 for serum samples from the two case-patients. Values near the Western blot indicate the ratio between the signal obtained for the band compared to that from the positive control (see Supporting information). CA, capside; Env, envelope; gp, glycoprotein; IN, integrase; MA, matrix; Pos., positive control; Neg., negative control; su, subunit; RT, reverse transcriptase. (b) Seroneutralization by the case-patients’ serum of infection of peripheral blood mononuclear cells from HIV-negative donors by HIV-1 strain NL4.3. Ct, PCR cycle threshold; PBMCs, peripheral blood mononuclear cells. (c) Infectability of peripheral blood mononuclear cells from case-patients by the HIV-1 strain NL4.3. Ct, PCR cycle threshold; PBMCs, peripheral blood mononuclear cells. Clinical Microbiology and Infection 2014 20, 1280-1288DOI: (10.1111/1469-0691.12807) Copyright © 2014 European Society of Clinical Infectious Diseases Terms and Conditions

FIG. 2 HIV genome retrieved from case-patient no. 1. HIV genes are shown on the outer ring. On the inner rings, blue lines indicate tryptophan (W) codons in genes; red lines indicate W-to-stop mutations. Representation was built using DNAplotter (http://www.sanger.ac.uk/Software/Artemis/circular/). Clinical Microbiology and Infection 2014 20, 1280-1288DOI: (10.1111/1469-0691.12807) Copyright © 2014 European Society of Clinical Infectious Diseases Terms and Conditions

FIG. 3 Flow cytometric profiles of T cells of case no. 2. (a) Ex vivo phenotype of T cells. Differentiation (CD45RA, CCR7), activation (CD38, HLADR) and cytotoxic (Granzyme B, Perforin) markers were used to analyse CD4 (upper panel) and CD8 (lower panel) T cells. (b) Intracellular cytokine staining after 8 days of PBMC culture with a pool of 36 HIV-1 peptides. HIV-specific CD4+ (upper panel) and CD8+ (lower panel) T cells able to produce IFNγ, TNFα and/or MIP1β. Plots are gated on viable CD3+ CD4+ or CD4+CD8+ T cells, respectively. Clinical Microbiology and Infection 2014 20, 1280-1288DOI: (10.1111/1469-0691.12807) Copyright © 2014 European Society of Clinical Infectious Diseases Terms and Conditions

FIG. 4 Schematic of hypotheses for tryptophan (W)-to-stop codon mutations, and HIV cure, in the two case-patients. W-to-stop codon mutations may occur due to increased APOBEC3G activity (including that mediated, or boosted, by vif gene knockout) (a), errors of the cellular RNA polymerase (b) or DNA polymerase (c). Clinical Microbiology and Infection 2014 20, 1280-1288DOI: (10.1111/1469-0691.12807) Copyright © 2014 European Society of Clinical Infectious Diseases Terms and Conditions