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.
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+.


CONCLUSIONS
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.
Department of Immunobiology, College of Medicine, University of Arizona, Tucson, AZ 85724, USA. vsvaradan@yahoo.com
Vasudha
V
Sundaravaradan
Suman R
SR
Das
Rajesh
R
Ramakrishnan
Shobha
S
Sehgal
Sarla
S
Gopalan
Nafees
N
Ahmad
Shahid
S
Jameel
D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D002460:Cell Line; D005260:Female; D015726:Giant Cells / Q000276:immunology / Q000821:virology; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015658:HIV Infections / Q000097:blood / Q000276:immunology / Q000821:virology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D008264:Macrophages / Q000276:immunology / Q000821:virology*; D008297:Male; D008969:Molecular Sequence Data; D019713:Receptors, CCR5 / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D019718:Receptors, CXCR4 / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology / Q000821:virology*; D053586:Virus Internalization; D014779:Virus Replication
C527276:CXCR4 protein, human; D015699:HIV Envelope Protein gp120; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D011993:Recombinant Fusion Proteins; C514793:gp120 protein, Human immunodeficiency virus 1