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Journal of Virology, September 2000, p. 8494-8501, Vol. 74, No. 18
UNC Center for AIDS
Research1 and Department of Biochemistry
and Biophysics,2 University of North Carolina at
Chapel Hill, Chapel Hill, North Carolina 27599, and Department
of Pathology and Laboratory Medicine, University of Pennsylvania,
Philadelphia, Pennsylvania 191043
Received 1 December 1999/Accepted 13 June 2000
We have used a V3-specific heteroduplex tracking assay (V3-HTA)
with probes from two different human immunodeficiency virus type 1 (HIV-1) subtypes to examine the extent and pace of HIV-1 evolution late
in infection. Twenty-four subjects with advanced HIV-1 infection
(CD4+ T-cell count, <100/µl) and stable viral loads were
studied using blood plasma samples collected over a study period of
approximately 9 months, during which time most of the subjects were
treated with reverse transcriptase inhibitors. The V3-HTA patterns from the first and last time points were evaluated initially to determine the amounts of change in V3 sequence populations, which were primarily changes in abundance in preexisting sequence populations. Three of the
24 subjects had major changes (greater than 50% total change in the
relative abundance of the sequence populations), 11 subjects had
intermediate changes (10 to 50% total change), and 10 subjects had
minimal changes (less than 10% total change). The average total amount
of change was between two- and threefold greater in subjects with
X4-like variants, although there was no correlation between average
viral load and the presence of X4-like variants. V3-HTA patterns in
monthly samples from 11 of the subjects were also compared. In two
subjects, the amount of change exceeded 40% in a 1-month period.
Overall, the pace of change in V3 populations varied between subjects
and was not constant within a subject over time. Sequence analysis of
the V3 variants showed that R5-like variants (not containing any
X4-associated substitutions) continued to be maintained in three
subjects in the presence of X4-like variants, indicating that X4
variants do not always outgrow R5 variants. The coreceptor usage of the
V3 sequences from two subjects was determined using a cell fusion
assay. One subject had an X4 variant that was maintained at a low level
for at least 9 months, during which time the predominant variants were
R5X4 (dualtropic), while in the second subject the reverse situation
was observed. One of the dualtropic variants had a novel sequence motif
in V3, suggesting another evolutionary pathway to altered tropism.
These studies begin to probe the complexities and pace of V3 evolution in vivo, revealing dynamic patterns of change among multiple V3 sequence variants in a subset of subjects.
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Patterns of Changes in Human Immunodeficiency Virus
Type 1 V3 Sequence Populations Late in Infection
*
Corresponding author. Mailing address: 22-006 Lineberger Cancer Center, CB#7295, 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, September 2000, p. 8494-8501, Vol. 74, No. 18
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
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