A recent outbreak of human immunodeficiency virus type 1 infection in southern China was initiated by two highly homogeneous, geographically separated strains, circulating recombinant form AE and a novel BC recombinant - PubMed (original) (raw)

. 2000 Dec;74(23):11286-95.

doi: 10.1128/jvi.74.23.11286-11295.2000.

F E McCutchan, J K Carr, E Sanders-Buell, W Liu, J Chen, R Wagner, H Wolf, Y Shao, S Lai, C Beyrer, X F Yu

Affiliations

A recent outbreak of human immunodeficiency virus type 1 infection in southern China was initiated by two highly homogeneous, geographically separated strains, circulating recombinant form AE and a novel BC recombinant

S Piyasirisilp et al. J Virol. 2000 Dec.

Abstract

New outbreaks of human immunodeficiency virus type 1 (HIV-1) among injecting drug users (IDUs) are spreading in China along heroin trafficking routes. Recently, two separate HIV-1 epidemics among IDUs were reported in Guangxi, Southern China, where partial sequencing of the env gene showed subtype C and circulating recombinant form (CRF) AE. We evaluated five virtually full-length HIV-1 genome sequences from IDUs in Guangxi to determine the genetic diversity and the presence of intersubtype recombinants. Sequence analysis showed two geographically separated, highly homogeneous HIV-1 strains. B/C intersubtype recombinants were found in three IDUs from Baise City, in a mountainous region near the Yunnan-Guangxi border. These were mostly subtype C, with portions of the capsid and reverse transcriptase (RT) genes from subtype B. The subtype B portion of the capsid was located in the N-terminal domain, which has been shown to influence virus core maturation, virus infectivity, and binding to cyclophilin A, whereas the subtype B portion of RT was located in the palm subdomain, which is the active site of the enzyme. These BC recombinants differed from a BC recombinant found in Xinjiang Province in northwestern China. CRF AE strains were found in IDUs from Nanning, the capital of Guangxi, and in IDUs from Pingxiang City near the China-Vietnam border. The AE and BC recombinants were both remarkable for their low interpatient diversity, less than 1% for the full genome. Rapid spread of HIV-1 among IDUs may foster the emergence of highly homogeneous strains, including novel recombinants in regions with multiple subtypes.

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Figures

FIG. 1

FIG. 1

(A) Phylogenetic analysis of virtually full-length genome sequences. The tree was constructed by the neighbor-joining method, and the number at each node indicates the percent bootstrap support from 100 bootstrap resamplings. The Chinese sequences (97CNGX-2F, -6F, -7F, -9F, and -11F) are shown in boldface. Subtype designations are shown in capital letters (A to J). The scale bar represents 10% difference. (B) Bar plot showing interpatient HIV-1 diversity across the entire genome or individual genes among Chinese isolates from IDUs compared with HIV-1 sequences from patients with heterosexual transmission. The interpatient genetic distances were calculated using the Kimura two-parameter distance measurement in the DNA DIST part of the PHYLIP package and are expressed as the average genetic distance for all pairwise combinations of nucleotide sequences from patients within each group. AE-IDU (horizontal) were Chinese CRF AE strains (97CNGX-2F and -11F) from two IDUs in Pingxiang City and Nanning City, and BC-IDU (vertical) were Chinese BC recombinants (97CNGX-6F, -7F, and -9F) from three IDUs in Baise City. Two groups of reference strains were included: C-Heterosexual (diagonal) were subtype C strains from eight patients with heterosexual transmission in Gaborone, Botswana (24), and A-Heterosexual (grid) were subtype A strains from six Africans in Sweden who were infected in Uganda, Somalia, and Tanzania by heterosexual contact (3).

FIG. 2

FIG. 2

Detection of (A) novel BC recombinant 97CNGX-6F and (B) CRF AE 97CNGX-2F by distance scanning and bootscanning. The genetic distances between unknown isolate and each reference subtype were calculated for distance scanning with maximum likelihood. The x axis is the nucleotide position in the multiple alignment of the full-length HIV-1 sequences, and the y axis is the genetic distance. The distances between the unknown and the reference subtype A (green), subtype B (yellow), subtype B′ (red), subtype C (blue), subtype D (orange), CRF AE (brown), subtype F (light orange), subtype G (light green), subtype H (gray), and subtype J (black) were plotted. The reference subtypes are indicated in the box. The bootscanning of the unknown isolate and the reference subtypes was performed using the algorithm of maximum parsimony. The x axis is the nucleotide position in the multiple alignment of the full-length HIV-1 sequences, and the y axis is the bootstrap value (percent). The reference subtype B′ (red), subtype C (blue), CRF AE (brown), and subtype J (black) are indicated in the box. The recombination breakpoints were used to deduce the subtype structure of the virus as shown below the bootscan. The phylogenetic trees of the segments between the breakpoints (designated segments I to VI) of 97CNGX-6F were constructed by the neighbor-joining method with bootstrap values (percent) at the nodes with the unknown isolate.

FIG. 3

FIG. 3

Alignments of the deduced amino acid sequences of a BC recombinant (97CNGX-6F), subtype B, and subtype C in the region of (A) p24 capsid and (B) RT. The comparison was done for fragments extending from 200 bp upstream to 200 bp downstream of the putative recombination breakpoints of 97CNGX-6F in the gag and pol genes (from nucleotide positions 404 to 1254 and 2040 to 2738 of HIV-1RL42, corresponding to amino acid residue 82 of p17 matrix to residue 232 of p24 capsid and residues 36 to 267 of RT, respectively). RL42 is the subtype B′ prevalent in southern China (12). The consensus sequence of subtype C was derived from Indian subtype C strains (93IN301904, 93IN301905, 93IN301999, 94IN11246, and 95IN21068) (17). 94IN11246 was randomly chosen to represent Indian subtypes C (17). Dashes represent identity with the consensus sequences of subtype C. Dots represent gaps. X indicates the nonconsensus amino acid of Indian subtype C. Amino acids of 97CNGX-6F that were similar to RL42 but different from consensus subtype C are shown in boldface. Amino acid positions are shown above the protein sequences. Empty boxes indicate subtype B segments between the recombination breakpoints of 97CNGX-6F estimated by bootscanning. The cyclophilin A binding motif (vertical gray box) and major homology region (horizontal gray box) of p24 capsid and highly conserved aspartate residues 110, 185, and 186 of RT (gray box) are shown.

FIG. 4

FIG. 4

(A) Deduced subtype structure of the full-length HIV-1 genome of BC recombinants from Guangxi and Xinjiang provinces. 97CNGX-6F from Guangxi was mostly subtype C (gray) with portions of gag (p24 capsid) and pol (RT) genes from subtype B (vertical), whereas c54 from Xinjiang was subtype C with portions of gag (p6-protease), pol (RT), and vpr-env genes from subtype B. (B) Recombination breakpoints of BC recombinants in the region of RT estimated by bootscanning and subtype signature identification. B, subtype B (vertical); C, subtype C (gray); ND, undetermined fragment indicating the subtype switching zone (diagonal). Nucleotide positions are shown below the deduced subtype structure and refer to the position in reference strain HIV-1RL42 (12). Conserved aspartate residues 110, 185, and 186 of RT are marked D. The numbers of the subtype B or C signatures over the total signature site in that fragment are shown below the nucleotide positions. (C) Phylogenetic trees of RT segments from BC recombinants and reference strains were constructed by the neighbor-joining method with bootstrap values at the nodes. The 173-bp segment (between nucleotide positions 2365 and 2538 of HIV-1RL42) was the minimal overlapping region between 97CNGX-6F and c54 in the RT region. The longer 275-bp segment (between nucleotide positions 2303 and 2578 of HIV-1RL42) was derived from the midpoint of upstream recombination breakpoints (position 2241 of 97CNGX-6F and position 2365 of c54) and the midpoint of downstream breakpoints (position 2538 of 97CNGX-6F and position 2613 of c54). Isolates 97CNGX-6F and c54 are shown in boldface.

FIG. 5

FIG. 5

Heroin trafficking routes in southeast Asia. The dotted area indicates the opium-growing areas in Myanmar and Laos. The arrows indicate potential drug-trafficking routes. At least three drug-trafficking routes were associated with HIV-1 infection in China: from Yunnan through the Yunnan-Guangxi border city of Baise and through Nanning City, the capital city of Guangxi; from Myanmar and Laos to northern Vietnam, and then across the China-Vietnam border to Pingxiang City; and from Yunnan to west and northwest China.

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