title: High replication fitness and transmission efficiency of HIV-1 subtype C from India: Implications for subtype C predominance.
abstract: HIV-1 subtype C has been the predominant subtype throughout the course of the HIV-1 epidemic in India regardless of the geographic region of the country. In an effort to understand the mechanism of subtype C predominance in this country, we have investigated the in vitro replication fitness and transmission efficiency of HIV-1 subtypes A and C from India. Using a dual infection growth competition assay, we found that primary HIV-1 subtype C isolates had higher overall relative fitness in PBMC than subtype A primary isolates. Moreover, in an ex vivo cervical tissue derived organ culture, subtype C isolates displayed higher transmission efficiency across cervical mucosa than subtype A isolates. We found that higher fitness of subtype C was not due to a trans effect exerted by subtype C infected PBMC. A half genome A/C recombinant clone in which the 3' half of the viral genome of subtype A was replaced with the corresponding subtype C3' half, had similar replicative fitness as the parental subtype A. These results suggest that the higher replication fitness and transmission efficiency of subtype C virus compared to subtype A virus from India is most probably not due to the envelope gene alone and may be due to genes present within the 5' half of the viral genome or to a more complex interaction between the genes located within the two halves of the viral genome. These data provide a model to explain the asymmetric distribution of subtype C over other subtypes in India.
authors.affiliation: Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, 426 Parran Hall, GSPH, 130 DeSoto Street, Pittsburgh, PA 15261, USA.
authors.forename: Milka A
authors.initials: MA
authors.lastname: Rodriguez
authors.forename: Ming
authors.initials: M
authors.lastname: Ding
authors.forename: Deena
authors.initials: D
authors.lastname: Ratner
authors.forename: Yue
authors.initials: Y
authors.lastname: Chen
authors.forename: Srikanth P
authors.initials: SP
authors.lastname: Tripathy
authors.forename: Smita S
authors.initials: SS
authors.lastname: Kulkarni
authors.forename: Ramdas
authors.initials: R
authors.lastname: Chatterjee
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Tarwater
authors.forename: Phalguni
authors.initials: P
authors.lastname: Gupta
mesh_terms: D000293:Adolescent; D000328:Adult; D005260:Female; D016679:Genome, Viral / Q000235:genetics; D015658:HIV Infections / Q000235:genetics / Q000635:transmission* / Q000821:virology*; D015497:HIV-1 / Q000145:classification* / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology; D006801:Humans; D007194:India; D007963:Leukocytes, Mononuclear / Q000821:virology; D008297:Male; D008875:Middle Aged; D009924:Organ Culture Techniques; D012367:RNA, Viral / Q000378:metabolism; D014779:Virus Replication; D055815:Young Adult
chemical_list: D012367:RNA, Viral