TY - JOUR
T1 - High replication fitness and transmission efficiency of HIV-1 subtype C from India
T2 - Implications for subtype C predominance
AU - Rodriguez, Milka A.
AU - Ding, Ming
AU - Ratner, Deena
AU - Chen, Yue
AU - Tripathy, Srikanth P.
AU - Kulkarni, Smita S.
AU - Chatterjee, Ramdas
AU - Tarwater, Patrick M.
AU - Gupta, Phalguni
N1 - Funding Information:
We thank Kathy Kulka and Mary White for technical assistance. This work was supported by AIDS-FIRCA grant R03 TH00971 (PG), and RA10 65392A (PG). MR is supported by a minority supplement to the grant A151661 (Sharon Hillier).
PY - 2009/3/15
Y1 - 2009/3/15
N2 - 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.
AB - 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.
KW - HIV-1 replication fitness
KW - HIV-1 subtype C from India
KW - HIV-1 transmission
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U2 - 10.1016/j.virol.2008.12.025
DO - 10.1016/j.virol.2008.12.025
M3 - Article
C2 - 19157481
AN - SCOPUS:60649107795
SN - 0042-6822
VL - 385
SP - 416
EP - 424
JO - Virology
JF - Virology
IS - 2
ER -