Virus immunocapture provides evidence of CD8 lymphocyte-derived HIV-1 in vivo.
OBJECTIVE
To demonstrate that HIV-1 immunocapture with an antibody against CD8 specifically captures virions derived from infected CD8 T cells, and to determine the proportion of HIV-1 derived from CD8 lymphocytes in plasma samples from HIV-infected individuals.


METHODS
A virus capture method was developed to enable the detection of HIV-1 virions based upon the presence of certain cell-specific host-derived proteins (CD8, CD3, CD36) within the viral envelope. HIV-1 virions were captured using antibodies against these proteins and levels of bound virus were determined by quantitative reverse transcriptase-polymerase chain reaction. Highly pure CD8 and CD3+CD8- T-cell cultures were used as in-vitro models to determine the specificity of the virus capture technique.


RESULTS
The in-vitro model demonstrates that incorporation of the CD8 molecule into released virions is specific to infection of CD8 T cells. Levels of HIV-1 immunocaptured from plasma of infected individuals using the anti-CD8 antibody indicate that up to 15% (range 10-33) of the plasma viral load is derived from CD8 lymphocytes.


CONCLUSIONS
This study demonstrates for the first time that HIV-1-infected CD8 T cells can contribute substantially to levels of circulating virus during the course of infection. Levels of CD8-derived virus did not correlate with the level of infection of circulating CD8 T cells, but do show a significantly good fit to plasma viral loads based on a power model. The extensive infection of CD8 T cells implied by these results may contribute towards immune dysfunction and disease progression to AIDS.
Hughes
Gareth J
GJ
Centre for Infectious Diseases, University of Edinburgh, Summerhall, Edinburgh, UK. gareth.hughes@ed.ac.uk
Willey
Samantha J
SJ
Cochrane
Alexandra
A
Leen
Clifford
C
Bell
Jeanne E
JE
Simmonds
Peter
P
D018791:CD4 Lymphocyte Count; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology*; D002478:Cells, Cultured; D018450:Disease Progression; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification*; D006801:Humans; D011533:Proviruses / Q000302:isolation & purification; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000821:virology; D019562:Viral Load; D014771:Virion / Q000302:isolation & purification