Molecular Characterization of HIV-1 Subtype E in Vietnam: Evidence for Founder Effect

             As part of our continued commitment to promoting international collaboration on AIDS, conducted with our colleagues from Hanoi Medical College in Hanoi and the UCLA School of Public Health in Los Angeles, we have characterized the HIV-1 subtypes circulating among CSW and IDU in Vietnam.  A 325-nucleotide region spanning the V3 loop of the HIV-1 gp120-encoding env gene was amplified and sequenced from DNA extracted from filter paper-blotted blood samples collected between April 1995 and September 1995 from 8 CSW and 16 IDU from Can Tho, Nha Trang, Ho Chi Minh City, Hanoi and An Giang province.  Sequence alignment and comparison indicated that the Vietnam HIV-1 strains did not segregate according to local residence of the study participant.  The interstrain genetic diversity was higher among HIV-1 strains from CSW (n = 8; mean, 5.8 ± 1.8%; range, 2.2-9.0%) than among strains from IDU (n = 16; mean, 3.5 ± 1.9%; range, 0.3-6.9%).  In further analyzing the V3 loop, we found an amino acid-altering nucleotide substitution, resulting in a change from isoleucine (I) to methionine (M) just before the crown tetrapeptide GPGQ, in 14/24 (58%), 2/4 (50%) and 7/87 (8%) HIV-1 subtype E strains from Vietnam, Cambodia and Thailand, respectively.  Among the Vietnam HIV-1 strains, this M substitution was found more frequently among IDU (12/16, 75%) than CSW (2/8, 25%).  Moreover, an asparagine (N) deletion in the FNNKT motif (second N-linked glycosylation site in the C3 region) occurred frequently in the Vietnam HIV-1 strains when compared with 87 subtype E sequences from Thailand [54.2% vs. 26.4%; odds ratio (OR), 3.29; 95% confidence interval (CI), 1.18-9.29].  The occurrence of both the M substitution and N deletion was strongly associated with subtype E sequences from Vietnam, compared to 87 subtype E sequences from Thailand (50% vs. 1.1%; OR, 86.0; 95% CI, 10.35-3715.26).  Phylogenetic analysis, based on 61 residues spanning the 5â cysteine of the V3 loop to the FNNKT motif, demonstrated that all IDU and only CSW with the M substitution and/or N deletion formed a monophyletic group.  Collectively, our sequence and phylogenetic analyses of HIV-1 strains from Vietnam support a founder effect.  Moreover, the M substitution in the V3 loop and N deletion in the C3 region may serve as genetic markers to trace the spread of HIV-1 in southeast Asia.  Blood samples collected in April 1997 are currently being analyzed to ascertain the trends of HIV-1 genetic diversity in Vietnam.

Nerurkar, V.R., Nguyen, H.T., Dashwood, M., Hoffmann, P.R., Yin, C.Q., Morens, D., Kaplan, A.H., Detels, R., and Yanagihara, R.:  HIV type 1 E in commercial sex workers and injection drug users in southern Vietnam. AIDS Research and Human Retroviruses 1996;12:841-843.

Nerurkar, V.R., Nguyen, H.T., Woodward, C.L., Hoffmann, P.R., Dashwood, W-M., Long, H.T., Morens, D.M., Detels, R., and Yanagihara, R.:  Sequence and phylogenetic analyses of HIV-1 infection in Vietnam:  subtype E in commercial sex workers and injection drug users.  Cellular and Molecular Biology  1997;43:959-968.

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