Skip to main page content
U.S. flag

An official website of the United States government

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 1998 Oct;72(10):8240-51.
doi: 10.1128/JVI.72.10.8240-8251.1998.

Evolution of envelope sequences from the genital tract and peripheral blood of women infected with clade A human immunodeficiency virus type 1

M Poss  1 , A G Rodrigo, J J Gosink, G H Learn, D de Vange Panteleeff, H L Martin Jr, J Bwayo, J K Kreiss, J Overbaugh
Affiliations

Evolution of envelope sequences from the genital tract and peripheral blood of women infected with clade A human immunodeficiency virus type 1

M Poss et al. J Virol. 1998 Oct.

Abstract

The development of viral diversity during the course of human immunodeficiency virus type 1 (HIV-1) infection may significantly influence viral pathogenesis. The paradigm for HIV-1 evolution is based primarily on studies of male cohorts in which individuals were presumably infected with a single virus variant of subtype B HIV-1. In this study, we evaluated virus evolution based on sequence information of the V1, V2, and V3 portions of HIV-1 clade A envelope genes obtained from peripheral blood and cervical secretions of three women with genetically heterogeneous viral populations near seroconversion. At the first sample following seroconversion, the number of nonsynonymous substitutions per potential nonsynonymous site (dn) significantly exceeded substitutions at potential synonymous sites (ds) in plasma viral sequences from all individuals. Generally, values of dn remained higher than values of ds as sequences from blood or mucosa evolved. Mutations affected each of the three variable regions of the envelope gene differently; insertions and deletions dominated changes in V1, substitutions involving charged amino acids occurred in V2, and sequential replacement of amino acids over time at a small subset of positions distinguished V3. The relationship among envelope nucleotide sequences obtained from peripheral blood mononuclear cells, plasma, and cervical secretions was evaluated for each individual by both phylogenetic and phenetic analyses. In all subjects, sequences from within each tissue compartment were more closely related to each other than to sequences from other tissues (phylogenetic tissue compartmentalization). At time points after seroconversion in two individuals, there was also greater genetic identity among sequences from the same tissue compartment than among sequences from different tissue compartments (phenetic tissue compartmentalization). Over time, temporal phylogenetic and phenetic structure was detectable in mucosal and plasma viral samples from all three women, suggesting a continual process of migration of one or a few infected cells into each compartment followed by localized expansion and evolution of that population.

PubMed Disclaimer

Figures

FIG. 1
FIG. 1
Average intra-time point ds and dn for sequences from Q23, Q47, and Q45. At each time point, ds and dn were determined for sequences of the V1, V2, and V3 portions of the HIV-1 envelope gene that were obtained from cervical (Cx), plasma RNA (Rn), and PBMC (Pb) samples from each subject. Significant differences between dn and ds are indicated by ∗ (P < 0.05) and ∗∗ (P < 0.01).
FIG. 2
FIG. 2
Average inter-time point frequencies of ds and dn for sequences from Q23, Q47, and Q45. Values of dn and ds were determined by pairwise comparison between sequences from a tissue at each sample point and sequences obtained from that tissue at the seroconversion sample. The average difference between dn and ds, evaluated by t test, was significantly greater than zero for all Q23 tissues (P < 0.001 for all tissue isolates) and Q47 tissues (P < 0.05 for cervical [Cx], P < 0.005 for PBMC [Pb], and P < 0.05 for plasma RNA [Rn] samples) and for Q45 PBMC (P < 0.005) and plasma viral RNA (P < 0.001) sequences.
FIG. 3
FIG. 3
Phylogenetic trees derived from sequences obtained from Q23, Q47, and Q45. Trees were constructed by the neighbor-joining method. Sequences are represented by diamonds squares, and circles, for clones derived from PBMCs, plasma RNA, and cervical samples, respectively, containing a number that indicates the months PNS that the sample was taken. Branch lengths are drawn to scale. The scale bars represent 0.05 change per average nucleotide position.
FIG. 3
FIG. 3
Phylogenetic trees derived from sequences obtained from Q23, Q47, and Q45. Trees were constructed by the neighbor-joining method. Sequences are represented by diamonds squares, and circles, for clones derived from PBMCs, plasma RNA, and cervical samples, respectively, containing a number that indicates the months PNS that the sample was taken. Branch lengths are drawn to scale. The scale bars represent 0.05 change per average nucleotide position.
FIG. 3
FIG. 3
Phylogenetic trees derived from sequences obtained from Q23, Q47, and Q45. Trees were constructed by the neighbor-joining method. Sequences are represented by diamonds squares, and circles, for clones derived from PBMCs, plasma RNA, and cervical samples, respectively, containing a number that indicates the months PNS that the sample was taken. Branch lengths are drawn to scale. The scale bars represent 0.05 change per average nucleotide position.
FIG. 4
FIG. 4
Phylogenetic and phenetic evaluation of tissue as a character state for Q23, Q47, and Q45. Tree lengths were determined, as described in Materials and Methods, for 100 bootstrap trees and 100 randomly constructed trees. Tree topology for bootstrap trees was based on nucleotide sequence data of the V1, V2, and V3 portions of the envelope gene, but tree lengths were based on character state changes between tissues. The ratio of these tree lengths is plotted for each time point. Error bars indicate 1 standard deviation. Mantel’s test was used to determine phenetic relationships among tissue isolates. Time points at which tissue isolates are phenetically distinct are boxed, and levels of significance are indicated by ∗ (P < 0.05) and ∗∗ (P < 0.01).
FIG. 5
FIG. 5
Phylogenetic evaluation of time as a character state for Q23, Q47, and Q45. Tree lengths were determined, as described in Materials and Methods, for 100 bootstrap trees and 100 randomly constructed trees. Tree topology for bootstrap trees is based on nucleotide sequence data of the V1, V2, and V3 portions of the envelope gene, but tree lengths are based on character state changes between time points for cervical (Cx), plasma RNA (Rn), and PBMC (Pb) samples. The ratio of bootstrap to random tree lengths is plotted for each time point. Error bars indicate 1 standard deviation. Phenetic temporal structure was significant for sequences from all three tissues for Q23 (P < 0.001) and for Q47 and Q45 plasma viral RNA and cervical sequences (P < 0.001 and P < 0.05, respectively).
FIG. 6
FIG. 6
Changes in V3 seroconversion amino acid consensus sequences over time for Q23, Q47, and Q45. A reference consensus sequence was generated by determining the most common amino acid present at each position in all tissue isolates obtained at the seroconversion sample from each subject. For each subsequent time, the percentage of all sequences that contained an amino acid that differed from the reference sequence at each position is shown. Open and closed symbols represent years 1 and 2 after seroconversion, respectively. Characters (+, ×) are used if only one tissue compartment was sampled at a time point. The hatched bars represent changes in the final sample evaluated for each individual. Where more than 75% of sequences from the last sample contained a nonconsensus amino acid at a position, the replacement amino acid (single-letter designation) is given above the bar. Pb, PBMCs; Cx, cervical secretions.
FIG. 7
FIG. 7
Changes in predicted amino acid V1 sequence for Q23, Q47, and Q45. A consensus sequence was generated as described in the legend to Fig. 6 for all sequences from the seroconversion (A) and final (B) samples from cervical (Cx), plasma RNA (Rn), and PBMC (Pb) sequences from each subject. ∼, gap introduced to maintain alignment between the two consensus sequences; -, gap introduced to maintain alignment among the sequences from the same time point. Capital letters are used if more than 90% of the amino acids at that position are represented in the consensus, and a lowercase letter indicates that the amino acid is represented more than 50% of the time. Where no consensus occurs, “/” is used.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Albert J, Abrahamsson B, Nagy K, Aurelius E, Gaines H, Nystrom G, Fenyo E M. Rapid development of isolate-specific neutralizing antibodies after primary HIV-1 infection and consequent emergence of virus variants which resist neutralization by autologous sera. AIDS. 1990;4:107–112. - PubMed
    1. Arendrup M, Nielsen C, Hansen J-E S, Pedersen C, Mathiesen L, Nielsen J O. Autologous HIV-1 neutralizing antibodies: emergence of neutralization-resistant escape virus and subsequent development of escape virus neutralizing antibodies. J Acquired Immune Defic Syndr. 1992;5:303–307. - PubMed
    1. Balfe P, Simmonds P, Ludlam C A, Bishop J O, Leigh Brown A J. Concurrent evolution of human immunodeficiency virus type 1 in patients infected from the same source: rate of sequence change and low frequency of inactivating mutations. J Virol. 1990;64:6221–6233. - PMC - PubMed
    1. Barnett S W, Barboza A, Wilcox C M, Forsmark C E, Levy J A. Characterization of human immunodeficiency virus type 1 strains recovered from the bowel of infected individuals. Virology. 1991;182:802–809. - PubMed
    1. Bonhoeffer S, Holmes E C, Nowak M A. Causes of HIV diversity. Nature. 1995;376:125. . (Letter.) - PubMed

Publication types

Associated data

LinkOut - more resources