R5 human immunodeficiency virus type 1 (HIV-1) replicates more efficiently in primary CD4+ T-cell cultures than X4 HIV-1.
In this report, we present evidence that R5 human immunodeficiency virus type 1 (HIV-1) replicates more efficiently in primary CD4+ T cells than X4 HIV-1. By comparing CD3/CD28-costimulated CD4+ T-cell cultures infected by several X4 and R5 HIV-1 strains, we determined that R5-infected CD4+ T cells produce more virus over time than X4-infected CD4+ T cells. In the first comparison, we found that more cells were infected by the X4-tropic strain LAI than by the R5-tropic strain JR-CSF and yet that higher levels of viral production were detected in the R5-infected cultures. The differential viral production was partially due to the severe cytopathic effects of the X4 virus. We also compared cultures infected with the isogenic HIV-1 strains NL4-3 (X4) and 49.5 (R5). We found that fewer cells were infected by the R5 strain, and yet similar levels of viral production were detected in both infected cultures. Cell death played less of a role in the differential viral production of these strains, as the cell viability remained comparable in both X4- and R5-infected cultures over time. The final comparison involved the primary R5-tropic isolate KP1 and the primary dual-tropic isolate KP2. Although both strains infected similar numbers of cells and induced comparable levels of cytopathicity, viral production was considerably higher in the R5-infected culture. In summary, these data demonstrate that R5 HIV-1 has an increased capacity to replicate in costimulated CD4+ T cells compared to X4 HIV-1.
Schweighardt
Becky
B
Gladstone Institute of Virology and Immunology, University of California, San Francisco, California 94141-9100, USA. bschweighardt@gladstone.ucsf.edu
Roy
Ann-Marie
AM
Meiklejohn
Duncan A
DA
Grace
Edward J
EJ
Moretto
Walter J
WJ
Heymann
Jonas J
JJ
Nixon
Douglas F
DF
D018106:CD28 Antigens / Q000378:metabolism; D017252:CD3 Complex / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000378:metabolism / Q000821:virology*; D016923:Cell Death; D002455:Cell Division; D002470:Cell Survival; D002478:Cells, Cultured; D005434:Flow Cytometry; D015497:HIV-1 / Q000145:classification* / Q000502:physiology*; D006801:Humans; D054398:Receptors, CCR4; D019713:Receptors, CCR5 / Q000378:metabolism; D019707:Receptors, Chemokine / Q000378:metabolism; D014779:Virus Replication / Q000502:physiology*
C515354:CCR4 protein, human; D018106:CD28 Antigens; D017252:CD3 Complex; D054398:Receptors, CCR4; D019713:Receptors, CCR5; D019707:Receptors, Chemokine