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Journal of Virology, August 1999, p. 6271-6281, Vol. 73, No. 8
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Characterization of V3 Sequence Heterogeneity in Subtype C Human
Immunodeficiency Virus Type 1 Isolates from Malawi: Underrepresentation
of X4 Variants
Li-Hua
Ping,1,2
Julie
A. E.
Nelson,1
Irving F.
Hoffman,1,2
Jody
Schock,1,3
Suzanna L.
Lamers,4
Melissa
Goodman,1,2
Pietro
Vernazza,5
Peter
Kazembe,6
Martin
Maida,6
Dick
Zimba,6
Maureen M.
Goodenow,4
Joseph J.
Eron Jr.,1,2
Susan A.
Fiscus,1,3
Myron S.
Cohen,1,2 and
Ronald
Swanstrom1,7,*
UNC Center For AIDS
Research,1 Department of
Medicine,2 Department of Microbiology
and Immunology,3 and Department of
Biochemistry and Biophysics,7 University of
North Carolina at Chapel Hill, Chapel Hill, North Carolina;
Department of Pathology, Immunology, and Laboratory Medicine,
University of Florida College of Medicine, Gainesville,
Florida4; Institute for Clinical
Microbiology and Immunology, St. Gallen,
Switzerland5; and Lilongwe Central
Hospital, Lilongwe, Malawi6
Received 19 February 1999/Accepted 20 April 1999
We have examined the nature of V3 sequence variability among
subtype C human immunodeficiency virus type 1 (HIV-1) sequences from
plasma-derived viral RNA present in infected men from Malawi. Sequence
variability was assessed by direct sequence analysis of the V3 reverse
transcription-PCR products, examination of virus populations by a
subtype C V3-specific heteroduplex tracking assay (V3-HTA), and
selected sequence analysis of molecular clones derived from the PCR
products. Sequence variability in V3 among the subtype C viruses was
not associated with the presence of basic amino acid substitutions.
This observation is in contrast to that for subtype B HIV-1, where
sequence variability is associated with such substitutions, and these
substitutions are determinants of altered coreceptor usage.
Evolutionary variants in subtype C V3 sequences, as defined by the
V3-HTA, were not correlated with the CD4 level in the infected person,
while such a correlation was found with subtype B V3 sequences. Viruses
were isolated from a subset of the subjects; all isolates used CCR5 and
not CXCR4 as a coreceptor, and none was able to grow in MT-2 cells, a
hallmark of the syncytium-inducing phenotype that is correlated with
CXCR4 usage. The overall sequence variability of the subtype C V3
region was no greater than that of the conserved regions of gp120. This limited sequence variability was also a feature of subtype B V3 sequences that do not carry the basic amino acid substitutions associated with altered coreceptor usage. Our results indicate that
altered coreceptor usage is rare in subtype C HIV-1 isolates in
sub-Saharan Africa and that sequence variability is not a feature of
the V3 region of env in the absence of altered coreceptor usage.
*
Corresponding author. Mailing address: CB7295, Rm
22-006 Lineberger Bldg., University of North Carolina at Chapel Hill,
Chapel Hill, NC 27599. Phone: (919) 966-5710. Fax: (919) 966-8212. E-mail: risunc{at}med.unc.edu.
Journal of Virology, August 1999, p. 6271-6281, Vol. 73, No. 8
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
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