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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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Related in: MedlinePlus

Rooted maximum-likelihood trees illustrating the epidemiologic linkage between sequences from mother (green) and infant (blue) subjects within each transmission pair.The nucleotide sequences of env V1-V5 region from each pair were aligned with two unrelated outgroup HIV-1 subtype C sequences obtained from the Los Alamos HIV Sequence Database. The branch containing unrelated outgroup sequences are not shown for space considerations. Only bootstrap support values greater than 75 are shown for the major nodes segregating mother and infant subjects.
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pone-0009294-g002: Rooted maximum-likelihood trees illustrating the epidemiologic linkage between sequences from mother (green) and infant (blue) subjects within each transmission pair.The nucleotide sequences of env V1-V5 region from each pair were aligned with two unrelated outgroup HIV-1 subtype C sequences obtained from the Los Alamos HIV Sequence Database. The branch containing unrelated outgroup sequences are not shown for space considerations. Only bootstrap support values greater than 75 are shown for the major nodes segregating mother and infant subjects.

Mentions: To examine the evolutionary relationship of mother and infant sequences, maximum likelihood trees for each transmission pair were reconstructed. Phylogenetic analysis indicated clear epidemiological linkage between each mother and infant. This tree shape was consistent with the putative transmission events (Figure 2) where the infant population forms a distinct well-supported monophyletic cluster and is genetically less diverse than the maternal population. All but one infant's sequences are derived from a single branch of the maternal tree, suggesting a single variant being transmitted from the mother in 5 of the 6 transmission pairs. In the sixth, MIP2617, a single sequence branches differently on the tree from the bulk of infant sequences.


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)

Rooted maximum-likelihood trees illustrating the epidemiologic linkage between sequences from mother (green) and infant (blue) subjects within each transmission pair.The nucleotide sequences of env V1-V5 region from each pair were aligned with two unrelated outgroup HIV-1 subtype C sequences obtained from the Los Alamos HIV Sequence Database. The branch containing unrelated outgroup sequences are not shown for space considerations. Only bootstrap support values greater than 75 are shown for the major nodes segregating mother and infant subjects.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0009294-g002: Rooted maximum-likelihood trees illustrating the epidemiologic linkage between sequences from mother (green) and infant (blue) subjects within each transmission pair.The nucleotide sequences of env V1-V5 region from each pair were aligned with two unrelated outgroup HIV-1 subtype C sequences obtained from the Los Alamos HIV Sequence Database. The branch containing unrelated outgroup sequences are not shown for space considerations. Only bootstrap support values greater than 75 are shown for the major nodes segregating mother and infant subjects.
Mentions: To examine the evolutionary relationship of mother and infant sequences, maximum likelihood trees for each transmission pair were reconstructed. Phylogenetic analysis indicated clear epidemiological linkage between each mother and infant. This tree shape was consistent with the putative transmission events (Figure 2) where the infant population forms a distinct well-supported monophyletic cluster and is genetically less diverse than the maternal population. All but one infant's sequences are derived from a single branch of the maternal tree, suggesting a single variant being transmitted from the mother in 5 of the 6 transmission pairs. In the sixth, MIP2617, a single sequence branches differently on the tree from the bulk of infant sequences.

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