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Journal of Virology, December 2000, p. 11367-11376, Vol. 74, No. 23
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Characterization of a Virtually Full-Length Human
Immunodeficiency Virus Type 1 Genome of a Prevalent Intersubtype
(C/B') Recombinant Strain in China
Ling
Su,1,2
Marcus
Graf,1
Yuanzhi
Zhang,2
Hagen
von
Briesen,3
Hui
Xing,2
Josef
Köstler,1
Holger
Melzl,1
Hans
Wolf,1
Yiming
Shao,2 and
Ralf
Wagner1,*
Institute of Medical Microbiology, University
of Regensburg, D-93053 Regensburg,1 and
Georg-Speyer Haus, 60596 Frankfurt,3 Germany, and National AIDS
Reference Laboratory, Chinese Academy of Preventive Medicine, Xuan
Wu Qu, Bejing 100052, China2
Received 7 September 1999/Accepted 1 September 2000
A molecular epidemiology study was conducted among more than 100 human immunodeficiency virus type 1 (HIV-1) subtype C seropositive intravenous drug users (IDUs) from China. Genotyping based on the
envelope C2V3 coding region revealed the highest homology of the most
prevalent virus strains circulating throughout China to subtype C
sequences of Indian origin. Based on these results, a virtually
full-length genome representing the most prevalent class of clade C
strains circulating throughout China was directly amplified from
peripheral blood mononuclear cells of a selected HIV-infected IDU and
subcloned. Sequence analysis identified a mosaic structure, suggesting
extensive intersubtype recombination events between genomes of the
prevalent clade C and (B')-subtype Thai virus strains of that
geographic region. Recombinant Identification Program analysis and
phylogenetic bootstrapping suggested that there were 10 breakpoints (i)
in the gag-pol coding region, (ii) in vpr and
at the 3' end of the vpu gene, and (iii) in the
nef open reading frame. (B')-sequences therefore include
(i) several insertions in the gag-pol coding region; (ii)
3'-vpr, the complete vpu gene, and the first
exons of tat and rev; and (iii) the 5' half of
the nef gene. Breakpoints located in the
vpr/vpu coding region as well as in the nef
gene of 97cn54 were found at almost identical positions of all subtype
C strains isolated from IDUs living in different areas of China,
suggesting a common ancestor for the C/B' recombinant strains. More
than 50% of well-defined subtype B-derived cytotoxic T-lymphocyte
epitopes within Gag and Pol and 10% of the known epitopes in
Env were found to exactly match sequences within in this clade C/B'
chimeric reference strain. These results may substantially facilitate a
biological comparison of clade C-derived reference strains as well as
the generation of useful reagents supporting vaccine-related efforts in China.
*
Corresponding author. Mailing address: Institute of
Medical Microbiology, University of Regensburg, Franz-Josef-Strauss
Allee 11, 93053 Regensburg, Germany. Phone: 49 (0) 941 944 6452. Fax: 49 (0) 941 944 6402. E-mail:
ralf.wagner{at}klinik.uni-regensburg.de.
Journal of Virology, December 2000, p. 11367-11376, Vol. 74, No. 23
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
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