Dendritic cell-mediated HIV-1 infection of T cells demonstrates a direct relationship to plasma viral RNA levels.
OBJECTIVE
To examine the relationship between infectivity of HIV-1 variants in dendritic cell (DC)-mediated in trans infection of T cells and plasma viral RNA levels in infected subjects.


METHODS
HIV-1 was isolated from peripheral blood mononuclear cells of chronically infected individuals, typed for coreceptor usage, and viral replication were examined in monocyte-derived DCs-peripheral blood lymphocytes cocultures. The rate of p24 antigen production during the logarithmic phase of viral replication was determined by enzyme-linked immunosorbent assay. Additionally, nef variants were cloned and expressed in trans with a HIV luciferase vector and CCR5-tropic HIV-1 envelope, and infectivity was measured in DC-mediated capture-transfer assays.


RESULTS
Replication capacity of HIV-1 viral CCR5-tropic isolates in monocyte-derived dendritic cells-peripheral blood lymphocytes cocultures was linearly associated with the plasma viral RNA levels in a cohort of HIV-1-infected individuals exhibiting an inverse relationship between plasma viral RNA and CD4 cell count. Furthermore, infectivity activity of nef variants in context of DC-mediated enhanced infection of T cells also showed a linear relationship to plasma viral RNA levels.


CONCLUSIONS
These results illustrate that replication capacity of HIV-1 in DC T-cell cultures is a significant determinant of plasma viral RNA level. The data suggest that adaptation of HIV-1 to DC interactions with T cells influences the level of viral replication in the host.
Arora
Reetakshi
R
Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA.
Bull
Lara
L
Siwak
Edward B
EB
Thippeshappa
Rajesh
R
Arduino
Roberto C
RC
Kimata
Jason T
JT
D000328:Adult; D018791:CD4 Lymphocyte Count; D003713:Dendritic Cells / Q000821:virology*; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000276:immunology / Q000821:virology*; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008297:Male; D012367:RNA, Viral / Q000097:blood*; D019713:Receptors, CCR5 / Q000235:genetics; D013601:T-Lymphocytes / Q000821:virology*; D019562:Viral Load; D014779:Virus Replication / Q000502:physiology
D012367:RNA, Viral; D019713:Receptors, CCR5
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