CRF19_cpx is an evolutionary fit HIV-1 variant strongly associated with rapid progression to AIDS in Cuba

Background: Clinicians reported an increasing trend of rapid progression (RP) (AIDS within 3. years of infection) in Cuba. Methods: Recently infected patients were prospectively sampled, 52 RP at AIDS diagnosis (AIDS-RP) and 21 without AIDS in the same time frame (non-AIDS). 22 patients were sampled at AIDS diagnosis (chronic-AIDS) retrospectively assessed as >. 3. years infected. Clinical, demographic, virological, epidemiological and immunological data were collected. Pol and env sequences were used for subtyping, transmission cluster analysis, and prediction of resistance, co-receptor use and evolutionary fitness. Host, immunological and viral predictors of RP were explored through data mining. Findings: Subtyping revealed 26 subtype B strains, 6 C, 6 CRF18_cpx, 9 CRF19_cpx, 29 BG-recombinants and other subtypes/URFs. All patients infected with CRF19 belonged to the AIDS-RP group. Data mining identified CRF19, oral candidiasis and RANTES levels as the strongest predictors of AIDS-RP. CRF19 was more frequently predicted to use the CXCR4 co-receptor, had higher fitness scores in the protease region, and patients had higher viral load at diagnosis. Interpretation: CRF19 is a recombinant of subtype D (C-part of Gag, PR, RT and nef), subtype A (N-part of Gag, Integrase, Env) and subtype G (Vif, Vpr, Vpu and C-part of Env). Since subtypes D and A have been associated with respectively faster and slower disease progression, our findings might indicate a fit PR driving high viral load, which in combination with co-infections may boost RANTES levels and thus CXCR4 use, potentially explaining the fast progression. We propose that CRF19 is evolutionary very fit and causing rapid progression to AIDS in many newly infected patients in Cuba. © 2015.

• Fecha de publicación: 2015
• Institución: Universidad del Rosario
• Repositorio: Repositorio EdocUR - U. Rosario
• Idioma: eng
• OAI Identifier: oai:repository.urosario.edu.co:10336/19047
• Acceso en línea: http://repository.urosario.edu.co/handle/10336/19047
• Palabra clave: Crf19; Cuba; Hiv-1; Progression To Aids; Variant; Grupos sociales; Alpha Interferon; Beta 2 Microglobulin; Chemokine Receptor Ccr5; Chemokine Receptor Cxcr4; Cxcl9 Chemokine; Fas Ligand; Gamma Interferon; Gamma Interferon Inducible Protein 1; Granulocyte Colony Stimulating Factor; Interleukin 1; Interleukin 12P7; Interleukin 1Beta; Interleukin 2; Interleukin 4; Interleukin 5; Interleukin 6; Interleukin 8; Lymphotoxin; Macrophage Inflammatory Protein 1Alpha; Macrophage Inflammatory Protein 1Beta; Monocyte Chemotactic Protein 1; Neopterin; Rantes; Tumor Necrosis Factor Alpha; Pol Protein; Virus Envelope Protein; Acquired Immune Deficiency Syndrome; Adult; Antiviral Resistance; Article; Cd4 Lymphocyte Count; Controlled Study; Cuba; Disease Course; Enzyme Linked Immunosorbent Assay; Female; Genetic Analysis; Genetic Variability; Heterosexuality; Human; Human Immunodeficiency Virus 1 Infection; Immunity; Major Clinical Study; Male; Mixed Infection; Priority Journal; Prospective Study; Reproductive Fitness; Retrospective Study; Thrush; Virus Load; Virus Recombination; Virus Replication; Virus Transmission; Virus Typing; Young Adult; Acquired Immunodeficiency Syndrome; Drug Effects; Evolution; Genetic Variation; Genetics; Hiv Infections; Human Immunodeficiency Virus 1; Immunology; Pathogenicity; Sexual Behavior; Virology; Acquired Immunodeficiency Syndrome; Adult; Biological Evolution; Coinfection; Cuba; Drug Resistance, Viral; Env Gene Products, Human Immunodeficiency Virus; Female; Genetic Variation; Hiv Infections; Hiv-1; Humans; Male; Pol Gene Products, Human Immunodeficiency Virus; Retrospective Studies; Sexual Behavior; Viral Load; Young Adult; Enfermedad del sida; Personas VIH positivas
• License: Abierto (Texto Completo)