title: Transmission of Multiple HIV-1 Subtype C Transmitted/founder Viruses into the Same Recipients Was not Determined by Modest Phenotypic Differences.
abstract: 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.
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Hongshuo
authors.initials: H
authors.lastname: Song
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Bhavna
authors.initials: B
authors.lastname: Hora
authors.affiliation: Theoretical Division, Los Alamos National Laboratory, Los Alamos, NM 87545, USA.
authors.forename: Elena E
authors.initials: EE
authors.lastname: Giorgi
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Amit
authors.initials: A
authors.lastname: Kumar
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Fangping
authors.initials: F
authors.lastname: Cai
authors.affiliation: Theoretical Division, Los Alamos National Laboratory, Los Alamos, NM 87545, USA.
authors.forename: Tanmoy
authors.initials: T
authors.lastname: Bhattacharya
authors.affiliation: Theoretical Division, Los Alamos National Laboratory, Los Alamos, NM 87545, USA.
authors.forename: Alan S
authors.initials: AS
authors.lastname: Perelson
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.|National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun 130012, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
mesh_terms: D014644:Genetic Variation; D016679:Genome, Viral; D015658:HIV Infections / Q000635:transmission / Q000821:virology*; D015497:HIV-1 / Q000145:classification* / Q000235:genetics* / Q000502:physiology; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology; D008297:Male; D010641:Phenotype; D019713:Receptors, CCR5 / Q000502:physiology; D015728:Receptors, HIV / Q000502:physiology; D056189:Viral Tropism / Q000235:genetics; D014779:Virus Replication / Q000187:drug effects
chemical_list: C584933:CCR5 protein, human; D016898:Interferon-alpha; D019713:Receptors, CCR5; D015728:Receptors, HIV