Role of HIV-1 subtype C envelope V3 to V5 regions in viral entry, coreceptor utilization and replication efficiency in primary T-lymphocytes and monocyte-derived macrophages

Persistent Link:
http://hdl.handle.net/10150/610260
Title:
Role of HIV-1 subtype C envelope V3 to V5 regions in viral entry, coreceptor utilization and replication efficiency in primary T-lymphocytes and monocyte-derived macrophages
Author:
Sundaravaradan, Vasudha; Das, Suman; Ramakrishnan, Rajesh; Sehgal, Shobha; Gopalan, Sarla; Ahmad, Nafees; Jameel, Shahid
Affiliation:
Department of Immunobiology, College of Medicine, University of Arizona, Tucson, AZ 85724, USA; Virology Group, International Center for Genetic Engineering and Biotechnology, New Delhi, India; Departments of Pathology and Obstetrics and Gynecology, Post Graduate Institute of Medical Education and Research, Chandigarh, India; NIAID, National Institutes of Health, Bethesda, MD 20892, USA; Department of Molecular Virology & Microbiology, Baylor College of Medicine, Houston, TX 77030, USA
Issue Date:
2007
Publisher:
BioMed Central
Citation:
Virology Journal 2007, 4:126 doi:10.1186/1743-422X-4-126
Journal:
Virology Journal
Rights:
© 2007 Sundaravaradan 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:Several subtypes of HIV-1 circulate in infected people worldwide, including subtype B in the United States and subtype C in Africa and India. To understand the biological properties of HIV-1 subtype C, including cellular tropism, virus entry, replication efficiency and cytopathic effects, we reciprocally inserted our previously characterized envelope V3-V5 regions derived from 9 subtype C infected patients from India into a subtype B molecular clone, pNL4-3. Equal amounts of the chimeric viruses were used to infect T-lymphocyte cell lines (A3.01 and MT-2), coreceptor cell lines (U373-MAGI-CCR5/CXCR4), primary blood T-lymphocytes (PBL) and monocyte-derived macrophages (MDM).RESULTS:We found that subtype C envelope V3-V5 region chimeras failed to replicate in T-lymphocyte cell lines but replicated in PBL and MDM. In addition, these chimeras were able to infect U373MAGI-CD4+-CCR5+ but not U373MAGI-CD4+-CXCR4+ cell line, suggesting CCR5 coreceptor utilization and R5 phenotypes. These subtype C chimeras were unable to induce syncytia in MT-2 cells, indicative of non-syncytium inducing (NSI) phenotypes. More importantly, the subtype C envelope chimeras replicated at higher levels in PBL and MDM compared with subtype B chimeras and isolates. Furthermore, the higher levels subtype C chimeras replication in PBL and MDM correlated with increased virus entry in U373MAGI-CD4+-CCR5+.CONCLUSION:Taken together, these results suggest that the envelope V3 to V5 regions of subtype C contributed to higher levels of HIV-1 replication compared with subtype B chimeras, which may contribute to higher viral loads and faster disease progression in subtype C infected individuals than other subtypes as well as rapid HIV-1 subtype C spread in India.
EISSN:
1743-422X
DOI:
10.1186/1743-422X-4-126
Version:
Final published version
Additional Links:
http://www.virologyj.com/content/4/1/126

Full metadata record

DC FieldValue Language
dc.contributor.authorSundaravaradan, Vasudhaen
dc.contributor.authorDas, Sumanen
dc.contributor.authorRamakrishnan, Rajeshen
dc.contributor.authorSehgal, Shobhaen
dc.contributor.authorGopalan, Sarlaen
dc.contributor.authorAhmad, Nafeesen
dc.contributor.authorJameel, Shahiden
dc.date.accessioned2016-05-20T09:02:29Z-
dc.date.available2016-05-20T09:02:29Z-
dc.date.issued2007en
dc.identifier.citationVirology Journal 2007, 4:126 doi:10.1186/1743-422X-4-126en
dc.identifier.doi10.1186/1743-422X-4-126en
dc.identifier.urihttp://hdl.handle.net/10150/610260-
dc.description.abstractBACKGROUND:Several subtypes of HIV-1 circulate in infected people worldwide, including subtype B in the United States and subtype C in Africa and India. To understand the biological properties of HIV-1 subtype C, including cellular tropism, virus entry, replication efficiency and cytopathic effects, we reciprocally inserted our previously characterized envelope V3-V5 regions derived from 9 subtype C infected patients from India into a subtype B molecular clone, pNL4-3. Equal amounts of the chimeric viruses were used to infect T-lymphocyte cell lines (A3.01 and MT-2), coreceptor cell lines (U373-MAGI-CCR5/CXCR4), primary blood T-lymphocytes (PBL) and monocyte-derived macrophages (MDM).RESULTS:We found that subtype C envelope V3-V5 region chimeras failed to replicate in T-lymphocyte cell lines but replicated in PBL and MDM. In addition, these chimeras were able to infect U373MAGI-CD4+-CCR5+ but not U373MAGI-CD4+-CXCR4+ cell line, suggesting CCR5 coreceptor utilization and R5 phenotypes. These subtype C chimeras were unable to induce syncytia in MT-2 cells, indicative of non-syncytium inducing (NSI) phenotypes. More importantly, the subtype C envelope chimeras replicated at higher levels in PBL and MDM compared with subtype B chimeras and isolates. Furthermore, the higher levels subtype C chimeras replication in PBL and MDM correlated with increased virus entry in U373MAGI-CD4+-CCR5+.CONCLUSION:Taken together, these results suggest that the envelope V3 to V5 regions of subtype C contributed to higher levels of HIV-1 replication compared with subtype B chimeras, which may contribute to higher viral loads and faster disease progression in subtype C infected individuals than other subtypes as well as rapid HIV-1 subtype C spread in India.en
dc.language.isoenen
dc.publisherBioMed Centralen
dc.relation.urlhttp://www.virologyj.com/content/4/1/126en
dc.rights© 2007 Sundaravaradan 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.titleRole of HIV-1 subtype C envelope V3 to V5 regions in viral entry, coreceptor utilization and replication efficiency in primary T-lymphocytes and monocyte-derived macrophagesen
dc.typeArticleen
dc.identifier.eissn1743-422Xen
dc.contributor.departmentDepartment of Immunobiology, College of Medicine, University of Arizona, Tucson, AZ 85724, USAen
dc.contributor.departmentVirology Group, International Center for Genetic Engineering and Biotechnology, New Delhi, Indiaen
dc.contributor.departmentDepartments of Pathology and Obstetrics and Gynecology, Post Graduate Institute of Medical Education and Research, Chandigarh, Indiaen
dc.contributor.departmentNIAID, National Institutes of Health, Bethesda, MD 20892, USAen
dc.contributor.departmentDepartment of Molecular Virology & Microbiology, Baylor College of Medicine, Houston, TX 77030, USAen
dc.identifier.journalVirology Journalen
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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