The Genetic Diversity of HIV-1 Quasispecies Within Primary Infected Individuals

HIV has remarkable genetic diversity among populations. The diversity has critical impacts on transmission, immune escape, pathogenesis, and clinical management. HIV-1 diversity originates from frequent mutation and recombination during reverse transcription. This work focuses on the quasispecies genetic dynamics within individuals with primary infections. Eleven men who have sex with men from the Beijing PRIMO Clinical Cohort were identified as primary infection and had three or four series of their anticoagulant blood samples collected. Viral RNA was extracted and amplified using single-genome amplification. Products of the gp120 gene that met single-genome amplification requirements were sequenced. Subtype assortment of all collected sequences was performed using both the jumping profile hidden Markov model (jpHMM) and REGA. Quasispecies diversity at each time was estimated using Mega 6. Intrapatient recombination was analyzed using RDP4. According to the Fiebig classification system, YA-81 belongs to stage III and YA-113 belongs to stage IV. The other samples are all associated with the infection stage of V/VI. YA113 had a dual infection with subtype B and a new unique recombinant form involving CRF01_AE and C. The other eight were infected with CRF01_AE, one was infected with B/C recombinant, and the last one with B. Of the 10 single infections, 8 were caused by 1 founder virus. They all displayed a sharp increase of quasispecies diversity during the sampling times. Two were caused by at least two founder viruses. The diversity of these strains starts at a significantly high level and is followed by a relatively steady trend. Critically, the separate subtypes YA113-B and YA113-CRF01_AE/C both showed a similar trend to those infected by a single founder virus. Recombination analysis revealed that 5 of 11 cases underwent detectable intrapatient recombination. These findings indicate that tracing the dynamics of HIV-1 quasispecies during early infection may be relevant and valuable for understanding pathways of viral diversification and immune escape.