HIV-1 sequence evolution in vivo after superinfection with three viral strains

• Main Authors: van der Kuyl Antoinette C, Zorgdrager Fokla, Reiss Peter, Cornelissen Marion, Kozaczynska Karolina
• Format: Article
• Language: English
• Published: BMC 2007-08-01
• Series: Retrovirology
• Online Access: http://www.retrovirology.com/content/4/1/59

<p>Abstract</p> <p>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.</p> <p>The nucleotide evolution of <it>gag </it>and <it>env</it>-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 <it>gag </it>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 <it>env </it>gene showed that strain B2 and CRF01_AE RNA was present in equal amounts, while levels of strain B1 were 100-fold lower.</p> <p>All three strains were detected in seminal plasma, suggesting that simultaneous transmission is possible.</p>