Characterization of HIV-1 envelope gp41 genetic diversity and functional domains following perinatal transmission

Persistent Link:
http://hdl.handle.net/10150/610244
Title:
Characterization of HIV-1 envelope gp41 genetic diversity and functional domains following perinatal transmission
Author:
Ramakrishnan, Rajesh; Mehta, Roshni; Sundaravaradan, Vasudha; Davis, Tiffany; Ahmad, Nafees
Affiliation:
Department of Microbiology and Immunology, College of Medicine, The University of Arizona Health Sciences Center, Tucson, Arizona 85724, USA; Current Address : Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, 77030, USA
Issue Date:
2006
Publisher:
BioMed Central
Citation:
Retrovirology 2006, 3:42 doi:10.1186/1742-4690-3-42
Journal:
Retrovirology
Rights:
© 2006 Ramakrishnan et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0)
Collection Information:
This item is part of the UA Faculty Publications collection. For more information this item or other items in the UA Campus Repository, contact the University of Arizona Libraries at repository@u.library.arizona.edu.
Abstract:
BACKGROUND:HIV-1 envelope gp41 is a transmembrane protein that promotes fusion of the virus with the plasma membrane of the host cells required for virus entry. In addition, gp41 is an important target for the immune response and development of antiviral and vaccine strategies, especially when targeting the highly variable envelope gp120 has not met with resounding success. Mutations in gp41 may affect HIV-1 entry, replication, pathogenesis, and transmission. We, therefore, characterized the molecular properties of gp41, including genetic diversity, functional motifs, and evolutionary dynamics from five mother-infant pairs following perinatal transmission.RESULTS:The gp41 open reading frame (ORF) was maintained with a frequency of 84.17% in five mother-infant pairs' sequences following perinatal transmission. There was a low degree of viral heterogeneity and estimates of genetic diversity in gp41 sequences. Both mother and infant gp41 sequences were under positive selection pressure, as determined by ratios of non-synonymous to synonymous substitutions. Phylogenetic analysis of 157 mother-infant gp41 sequences revealed distinct clusters for each mother-infant pair, suggesting that the epidemiologically linked mother-infant pairs were evolutionarily closer to each other as compared with epidemiologically unlinked sequences. The functional domains of gp41, including fusion peptide, heptad repeats, glycosylation sites and lentiviral lytic peptides were mostly conserved in gp41 sequences analyzed in this study. The CTL recognition epitopes and motifs recognized by fusion inhibitors were also conserved in the five mother-infant pairs.CONCLUSION:The maintenance of an intact envelope gp41 ORF with conserved functional domains and a low degree of genetic variability as well as positive selection pressure for adaptive evolution following perinatal transmission is consistent with an indispensable role of envelope gp41 in HIV-1 replication and pathogenesis.
EISSN:
1742-4690
DOI:
10.1186/1742-4690-3-42
Version:
Final published version
Additional Links:
http://www.retrovirology.com/content/3/1/42

Full metadata record

DC FieldValue Language
dc.contributor.authorRamakrishnan, Rajeshen
dc.contributor.authorMehta, Roshnien
dc.contributor.authorSundaravaradan, Vasudhaen
dc.contributor.authorDavis, Tiffanyen
dc.contributor.authorAhmad, Nafeesen
dc.date.accessioned2016-05-20T09:02:04Z-
dc.date.available2016-05-20T09:02:04Z-
dc.date.issued2006en
dc.identifier.citationRetrovirology 2006, 3:42 doi:10.1186/1742-4690-3-42en
dc.identifier.doi10.1186/1742-4690-3-42en
dc.identifier.urihttp://hdl.handle.net/10150/610244-
dc.description.abstractBACKGROUND:HIV-1 envelope gp41 is a transmembrane protein that promotes fusion of the virus with the plasma membrane of the host cells required for virus entry. In addition, gp41 is an important target for the immune response and development of antiviral and vaccine strategies, especially when targeting the highly variable envelope gp120 has not met with resounding success. Mutations in gp41 may affect HIV-1 entry, replication, pathogenesis, and transmission. We, therefore, characterized the molecular properties of gp41, including genetic diversity, functional motifs, and evolutionary dynamics from five mother-infant pairs following perinatal transmission.RESULTS:The gp41 open reading frame (ORF) was maintained with a frequency of 84.17% in five mother-infant pairs' sequences following perinatal transmission. There was a low degree of viral heterogeneity and estimates of genetic diversity in gp41 sequences. Both mother and infant gp41 sequences were under positive selection pressure, as determined by ratios of non-synonymous to synonymous substitutions. Phylogenetic analysis of 157 mother-infant gp41 sequences revealed distinct clusters for each mother-infant pair, suggesting that the epidemiologically linked mother-infant pairs were evolutionarily closer to each other as compared with epidemiologically unlinked sequences. The functional domains of gp41, including fusion peptide, heptad repeats, glycosylation sites and lentiviral lytic peptides were mostly conserved in gp41 sequences analyzed in this study. The CTL recognition epitopes and motifs recognized by fusion inhibitors were also conserved in the five mother-infant pairs.CONCLUSION:The maintenance of an intact envelope gp41 ORF with conserved functional domains and a low degree of genetic variability as well as positive selection pressure for adaptive evolution following perinatal transmission is consistent with an indispensable role of envelope gp41 in HIV-1 replication and pathogenesis.en
dc.language.isoenen
dc.publisherBioMed Centralen
dc.relation.urlhttp://www.retrovirology.com/content/3/1/42en
dc.rights© 2006 Ramakrishnan et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0)en
dc.titleCharacterization of HIV-1 envelope gp41 genetic diversity and functional domains following perinatal transmissionen
dc.typeArticleen
dc.identifier.eissn1742-4690en
dc.contributor.departmentDepartment of Microbiology and Immunology, College of Medicine, The University of Arizona Health Sciences Center, Tucson, Arizona 85724, USAen
dc.contributor.departmentCurrent Address : Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, 77030, USAen
dc.identifier.journalRetrovirologyen
dc.description.collectioninformationThis item is part of the UA Faculty Publications collection. For more information this item or other items in the UA Campus Repository, contact the University of Arizona Libraries at repository@u.library.arizona.edu.en
dc.eprint.versionFinal published versionen
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