Restricted Genetic Diversity of HIV-1 Subtype C Envelope Glycoprotein from Perinatally Infected Zambian Infants

Hong Zhang, Damien C. Tully, Federico G. Hoffmann, Jun He, Chipepo Kankasa, Charles Wood

Research output: Contribution to journalArticle

24 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere0009294
JournalPloS one
Volume5
Issue number2
DOIs
StatePublished - Dec 1 2010

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Human immunodeficiency virus 1
HIV-1
glycoproteins
Glycoproteins
Viruses
viruses
genetic variation
Mothers
glycosylation
Glycosylation
selection intensity
phylogeny
infants
infection
glycoprotein gC, herpes simplex virus type 1
DNA sequences
Infection
Population
nucleotide sequences
therapeutics

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Restricted Genetic Diversity of HIV-1 Subtype C Envelope Glycoprotein from Perinatally Infected Zambian Infants. / Zhang, Hong; Tully, Damien C.; Hoffmann, Federico G.; He, Jun; Kankasa, Chipepo; Wood, Charles.

In: PloS one, Vol. 5, No. 2, e0009294, 01.12.2010.

Research output: Contribution to journalArticle

Zhang, Hong ; Tully, Damien C. ; Hoffmann, Federico G. ; He, Jun ; Kankasa, Chipepo ; Wood, Charles. / Restricted Genetic Diversity of HIV-1 Subtype C Envelope Glycoprotein from Perinatally Infected Zambian Infants. In: PloS one. 2010 ; Vol. 5, No. 2.
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