title: HIV-1 sequence evolution in vivo after superinfection with three viral strains.
abstract: With millions of people infected worldwide, the evolution of HIV-1 in vivo has been the subject of much research. Although recombinant viruses were detected early in the epidemic, evidence that HIV-1 dual infections really occurred came much later. Dual infected patients, consisting of coinfected (second infection before seroconversion) and superinfected (second infection after seroconversion) individuals, opened up a new area of HIV-1 evolution studies. Here, we describe the in-depth analysis of HIV-1 over time in a patient twice superinfected with HIV-1, first with a subtype B (B2) strain and then with CRF01_AE after initial infection with a subtype B (B1) strain. The nucleotide evolution of gag and env-V3 of the three strains followed a similar pattern: a very low substitution rate in the first 2-3 years of infection, with an increase in synonymous substitutions thereafter. Convergent evolution at the protein level was rare: only a single amino acid in a gag p24 epitope showed convergence in the subtype B strains. Reversal of CTL-epitope mutations were also rare, and did not converge. Recombinant viruses were observed between the two subtype B strains. Luciferase-assays suggested that the CRF01_AE long terminal repeat (LTR) constituted the strongest promoter, but this was not reflected in the plasma viral load. Specific real-time PCR assays based upon the env gene showed that strain B2 and CRF01_AE RNA was present in equal amounts, while levels of strain B1 were 100-fold lower. All three strains were detected in seminal plasma, suggesting that simultaneous transmission is possible.
authors: Laboratory of Experimental Virology, Department of Medical Microbiology, Centre for Infection and Immunity Amsterdam (CINIMA), Academic Medical Centre of the University of Amsterdam, Amsterdam, The Netherlands. k.kozaczynska@amc.uva.nl
authors: Karolina
authors: K
authors: Kozaczynska
authors: Marion
authors: M
authors: Cornelissen
authors: Peter
authors: P
authors: Reiss
authors: Fokla
authors: F
authors: Zorgdrager
authors: Antoinette C
authors: AC
authors: van der Kuyl
mesh_terms: D019943:Amino Acid Substitution / Q000235:genetics; D019143:Evolution, Molecular; D015686:Gene Products, env / Q000235:genetics / Q000276:immunology; D015683:Gene Products, gag / Q000235:genetics / Q000276:immunology; D016679:Genome, Viral / Q000235:genetics*; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification*; D006801:Humans; D020125:Mutation, Missense; D012367:RNA, Viral / Q000097:blood; D011995:Recombination, Genetic; D012661:Semen / Q000821:virology; D017422:Sequence Analysis, DNA; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D019562:Viral Load; D014766:Viremia / Q000821:virology
chemical_list: D015686:Gene Products, env; D015683:Gene Products, gag; D012367:RNA, Viral
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