Transmission of Multiple HIV-1 Subtype C Transmitted/founder Viruses into the Same Recipients Was not Determined by Modest Phenotypic Differences

• Published in: Scientific reports Vol. 6; no. 1; p. 38130
• Main Authors: Song, Hongshuo, Hora, Bhavna, Giorgi, Elena E., Kumar, Amit, Cai, Fangping, Bhattacharya, Tanmoy, Perelson, Alan S., Gao, Feng
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 02.12.2016; Nature Publishing Group
• Subjects: 45; 45/70; 60 APPLIED LIFE SCIENCES; 631/326/596/2563; 692/699/255/1901; CCR5 protein; CXCR4 protein; Disease transmission; Efficiency; Genetic Variation; Genome, Viral; Genomes; HIV Infections - transmission; HIV Infections - virology; HIV-1 - classification; HIV-1 - genetics; HIV-1 - physiology; Humanities and Social Sciences; Humans; Interferon; Interferon-alpha - pharmacology; Male; Mucosa; multidisciplinary; Phenotype; Receptors, CCR5 - physiology; Receptors, HIV - physiology; Reproductive fitness; Science; Science & Technology - Other Topics; Viral Tropism - genetics; Virus Replication - drug effects; Viruses
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep38130

A severe bottleneck exists during HIV-1 mucosal transmission. However, viral properties that determine HIV-1 transmissibility are not fully elucidated. We identified multiple transmitted/founder (T/F) viruses in six HIV-1-infected subjects by analyzing whole genome sequences. Comparison of biological phenotypes of different T/F viruses from the same individual allowed us to more precisely identify critical determinants for viral transmissibility since they were transmitted under similar conditions. All T/F viruses used coreceptor CCR5, while no T/F viruses used CXCR4 or GPR15. However, the efficiency for different T/F viruses from the same individual to use CCR5 was significantly variable, and the differences were even more significant for usage of coreceptors FPRL1, CCR3 and APJ. Resistance to IFN-α was also different between T/F viruses in 2 of 3 individuals. The relative fitness between T/F viruses from the same subject was highly variable (2–6%). Importantly, the levels of coreceptor usage efficiency, resistance to IFN-α and viral fitness were not associated with proportions of T/F viruses in each individual during acute infection. Our results show that the modest but significant differences in coreceptor usage efficiency, IFN-α sensitivity and viral fitness each alone may not play a critical role in HIV-1 transmission.