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Restricted genetic diversity of HIV-1 subtype C envelope glycoprotein from perinatally infected Zambian infants.

Zhang H, Tully DC, Hoffmann FG, He J, Kankasa C, Wood C - PLoS ONE (2010)

Bottom Line: Phylogenetic analysis indicates that most likely in all our infant subjects a single founder virus was responsible for establishing infection.Furthermore, the newly transmitted viruses from the infant had significantly fewer potential N-linked glycosylation sites in Env V1-V5 region and showed a propensity to encode shorter variable loops compared to the nontransmitted viruses.As a result the newly transmitted viruses are less diverse and harbored significantly less glycosylated envelope.

View Article: PubMed Central - PubMed

Affiliation: Nebraska Center for Virology, University of Nebraska, Lincoln, Nebraska, United States of America.

ABSTRACT

Background: Mother-to-child transmission of HIV-1 remains a significant problem in the resource-constrained settings where anti-retroviral therapy is still not widely available. Understanding the earliest events during HIV-1 transmission and characterizing the newly transmitted or founder virus is central to intervention efforts. In this study, we analyzed the viral env quasispecies of six mother-infant transmission pairs (MIPs) and characterized the genetic features of envelope glycoprotein that could influence HIV-1 subtype C perinatal transmission.

Methodology and findings: The V1-V5 region of env was amplified from 6 MIPs baseline samples and 334 DNA sequences in total were analyzed. A comparison of the viral population derived from the mother and infant revealed a severe genetic bottleneck occurring during perinatal transmission, which was characterized by low sequence diversity in the infant. Phylogenetic analysis indicates that most likely in all our infant subjects a single founder virus was responsible for establishing infection. Furthermore, the newly transmitted viruses from the infant had significantly fewer potential N-linked glycosylation sites in Env V1-V5 region and showed a propensity to encode shorter variable loops compared to the nontransmitted viruses. In addition, a similar intensity of selection was seen between mothers and infants with a higher rate of synonymous (dS) compared to nonsynonymous (dN) substitutions evident (dN/dS<1).

Conclusions: Our results indicate that a strong genetic bottleneck occurs during perinatal transmission of HIV-1 subtype C. This is evident through population diversity and phylogenetic patterns where a single viral variant appears to be responsible for infection in the infants. As a result the newly transmitted viruses are less diverse and harbored significantly less glycosylated envelope. This suggests that viruses with the restricted glycosylation in envelope glycoprotein appeared to be preferentially transmitted during HIV-1 subtype C perinatal transmission. In addition, our findings also indicated that purifying selection appears to predominate in shaping the early intrahost evolution of HIV-1 subtype C envelope sequences.

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Comparison of Env V1-V5 length between mother and infant variants.(A) Comparison of Env V1-V5 length for each transmission pair. The P value for each comparison between the mother and infant are shown. The horizontal bars indicate the mean value for each individual. (B) Comparison of Env V1-V5 length of the aggregate sequences from mothers and infants. The P value for the comparison between the mother and infant is shown. The box and whiskers plot denotes the median, minimum and maximum values.
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pone-0009294-g003: Comparison of Env V1-V5 length between mother and infant variants.(A) Comparison of Env V1-V5 length for each transmission pair. The P value for each comparison between the mother and infant are shown. The horizontal bars indicate the mean value for each individual. (B) Comparison of Env V1-V5 length of the aggregate sequences from mothers and infants. The P value for the comparison between the mother and infant is shown. The box and whiskers plot denotes the median, minimum and maximum values.

Mentions: We further examined the genetic features of Env which could influence HIV-1 subtype C MTCT such as the length of Env. Comparison of Env V1-V5 length of maternal and infant variants indicated that in four of the six MIPs (MIP 1084, 1449, 2669 and 2617), the infant sequences had a significant shorter V1-V5 length than those of their mothers (Table 1 and Figure 3A, P≤0.0096). In contrast, for the remaining two pairs (MIP2873 and 1984), a significant increase in V1-V5 length in the infant sequences was observed (Table 1 and Figure 3A, P≤0.0003). When the data was considered in aggregate, there were no significant differences in Env V1-V5 length between the mothers (median, 338; range, 326 to 356; n = 181) and the infants (median, 336; range, 319 to 356; n = 153) although there was a trend toward the infant sequences having shorter Env V1-V5 length compared to the maternal sequences (Fig. 3B, P = 0.0933). Similar observations were obtained when the analysis was confined to V1-V2 and V1-V4 region with the majority of infant sequences harboring significantly shorter lengths compared to maternal sequences (Table 2). However, both the mother and infant sequences contained 35 amino acids in V3 region. Another interesting observation from the sequence data is the distinct uniformity in the length of the envelope glycoprotein in the infants (Tables 1 and 2). This uniformity is seen in the V1-V5 (Table 1), V1-V4 (Table 2), and even V1-V2 loops (Table 2) in all except two infants, with infant 2669 displaying a range of sequence lengths in the V1-V5 domain (Tables 1), while infant 1084 having a range of sequence lengths in V1-V5 and V1-V4 region (Table 1 and Table 2).


Restricted genetic diversity of HIV-1 subtype C envelope glycoprotein from perinatally infected Zambian infants.

Zhang H, Tully DC, Hoffmann FG, He J, Kankasa C, Wood C - PLoS ONE (2010)

Comparison of Env V1-V5 length between mother and infant variants.(A) Comparison of Env V1-V5 length for each transmission pair. The P value for each comparison between the mother and infant are shown. The horizontal bars indicate the mean value for each individual. (B) Comparison of Env V1-V5 length of the aggregate sequences from mothers and infants. The P value for the comparison between the mother and infant is shown. The box and whiskers plot denotes the median, minimum and maximum values.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2823783&req=5

pone-0009294-g003: Comparison of Env V1-V5 length between mother and infant variants.(A) Comparison of Env V1-V5 length for each transmission pair. The P value for each comparison between the mother and infant are shown. The horizontal bars indicate the mean value for each individual. (B) Comparison of Env V1-V5 length of the aggregate sequences from mothers and infants. The P value for the comparison between the mother and infant is shown. The box and whiskers plot denotes the median, minimum and maximum values.
Mentions: We further examined the genetic features of Env which could influence HIV-1 subtype C MTCT such as the length of Env. Comparison of Env V1-V5 length of maternal and infant variants indicated that in four of the six MIPs (MIP 1084, 1449, 2669 and 2617), the infant sequences had a significant shorter V1-V5 length than those of their mothers (Table 1 and Figure 3A, P≤0.0096). In contrast, for the remaining two pairs (MIP2873 and 1984), a significant increase in V1-V5 length in the infant sequences was observed (Table 1 and Figure 3A, P≤0.0003). When the data was considered in aggregate, there were no significant differences in Env V1-V5 length between the mothers (median, 338; range, 326 to 356; n = 181) and the infants (median, 336; range, 319 to 356; n = 153) although there was a trend toward the infant sequences having shorter Env V1-V5 length compared to the maternal sequences (Fig. 3B, P = 0.0933). Similar observations were obtained when the analysis was confined to V1-V2 and V1-V4 region with the majority of infant sequences harboring significantly shorter lengths compared to maternal sequences (Table 2). However, both the mother and infant sequences contained 35 amino acids in V3 region. Another interesting observation from the sequence data is the distinct uniformity in the length of the envelope glycoprotein in the infants (Tables 1 and 2). This uniformity is seen in the V1-V5 (Table 1), V1-V4 (Table 2), and even V1-V2 loops (Table 2) in all except two infants, with infant 2669 displaying a range of sequence lengths in the V1-V5 domain (Tables 1), while infant 1084 having a range of sequence lengths in V1-V5 and V1-V4 region (Table 1 and Table 2).

Bottom Line: Phylogenetic analysis indicates that most likely in all our infant subjects a single founder virus was responsible for establishing infection.Furthermore, the newly transmitted viruses from the infant had significantly fewer potential N-linked glycosylation sites in Env V1-V5 region and showed a propensity to encode shorter variable loops compared to the nontransmitted viruses.As a result the newly transmitted viruses are less diverse and harbored significantly less glycosylated envelope.

View Article: PubMed Central - PubMed

Affiliation: Nebraska Center for Virology, University of Nebraska, Lincoln, Nebraska, United States of America.

ABSTRACT

Background: Mother-to-child transmission of HIV-1 remains a significant problem in the resource-constrained settings where anti-retroviral therapy is still not widely available. Understanding the earliest events during HIV-1 transmission and characterizing the newly transmitted or founder virus is central to intervention efforts. In this study, we analyzed the viral env quasispecies of six mother-infant transmission pairs (MIPs) and characterized the genetic features of envelope glycoprotein that could influence HIV-1 subtype C perinatal transmission.

Methodology and findings: The V1-V5 region of env was amplified from 6 MIPs baseline samples and 334 DNA sequences in total were analyzed. A comparison of the viral population derived from the mother and infant revealed a severe genetic bottleneck occurring during perinatal transmission, which was characterized by low sequence diversity in the infant. Phylogenetic analysis indicates that most likely in all our infant subjects a single founder virus was responsible for establishing infection. Furthermore, the newly transmitted viruses from the infant had significantly fewer potential N-linked glycosylation sites in Env V1-V5 region and showed a propensity to encode shorter variable loops compared to the nontransmitted viruses. In addition, a similar intensity of selection was seen between mothers and infants with a higher rate of synonymous (dS) compared to nonsynonymous (dN) substitutions evident (dN/dS<1).

Conclusions: Our results indicate that a strong genetic bottleneck occurs during perinatal transmission of HIV-1 subtype C. This is evident through population diversity and phylogenetic patterns where a single viral variant appears to be responsible for infection in the infants. As a result the newly transmitted viruses are less diverse and harbored significantly less glycosylated envelope. This suggests that viruses with the restricted glycosylation in envelope glycoprotein appeared to be preferentially transmitted during HIV-1 subtype C perinatal transmission. In addition, our findings also indicated that purifying selection appears to predominate in shaping the early intrahost evolution of HIV-1 subtype C envelope sequences.

Show MeSH
Related in: MedlinePlus