Induction of plasma (TRAIL), TNFR-2, Fas ligand, and plasma microparticles after human immunodeficiency virus type 1 (HIV-1) transmission: implications for HIV-1 vaccine design.
The death of CD4(+) CCR5(+) T cells is a hallmark of human immunodeficiency virus (HIV) infection. We studied the plasma levels of cell death mediators and products--tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), Fas ligand, TNF receptor type 2 (TNFR-2), and plasma microparticles--during the earliest stages of infection following HIV type 1 (HIV-1) transmission in plasma samples from U.S. plasma donors. Significant plasma TRAIL level elevations occurred a mean of 7.2 days before the peak of plasma viral load (VL), while TNFR-2, Fas ligand, and microparticle level elevations occurred concurrently with maximum VL. Microparticles had been previously shown to mediate immunosuppressive effects on T cells and macrophages. We found that T-cell apoptotic microparticles also potently suppressed in vitro immunoglobulin G (IgG) and IgA antibody production by memory B cells. Thus, release of TRAIL during the onset of plasma viremia (i.e., the eclipse phase) in HIV-1 transmission may initiate or amplify early HIV-1-induced cell death. The window of opportunity for a HIV-1 vaccine is from the time of HIV-1 transmission until establishment of the latently infected CD4(+) T cells. Release of products of cell death and subsequent immunosuppression following HIV-1 transmission could potentially narrow the window of opportunity during which a vaccine is able to extinguish HIV-1 infection and could place severe constraints on the amount of time available for the immune system to respond to the transmitted virus.
Duke Human Vaccine Institute, Department of Medicine, Duke University School of Medicine, Durham, North Carolina 27710, USA.
Nancy
N
Gasper-Smith
Deanna M
DM
Crossman
John F
JF
Whitesides
Nadia
N
Mensali
Janet S
JS
Ottinger
Steven G
SG
Plonk
M Anthony
MA
Moody
Guido
G
Ferrari
Kent J
KJ
Weinhold
Sara E
SE
Miller
Charles F
CF
Reich
Li
L
Qin
Stephen G
SG
Self
George M
GM
Shaw
Thomas N
TN
Denny
Laura E
LE
Jones
David S
DS
Pisetsky
Barton F
BF
Haynes
D000328:Adult; D000914:Antibodies, Viral / Q000096:biosynthesis; D001402:B-Lymphocytes / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D053222:Fas Ligand Protein / Q000097:blood*; D015658:HIV Infections / Q000276:immunology* / Q000821:virology*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D007108:Immune Tolerance; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000097:blood*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000097:blood*; D013997:Time Factors; D014481:United States; D019562:Viral Load
D000914:Antibodies, Viral; D053222:Fas Ligand Protein; D047889:Receptors, Tumor Necrosis Factor, Type II; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human