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.
Gasper-Smith
Nancy
N
Duke Human Vaccine Institute, Department of Medicine, Duke University School of Medicine, Durham, North Carolina 27710, USA.
Crossman
Deanna M
DM
Whitesides
John F
JF
Mensali
Nadia
N
Ottinger
Janet S
JS
Plonk
Steven G
SG
Moody
M Anthony
MA
Ferrari
Guido
G
Weinhold
Kent J
KJ
Miller
Sara E
SE
Reich
Charles F
CF
Qin
Li
L
Self
Stephen G
SG
Shaw
George M
GM
Denny
Thomas N
TN
Jones
Laura E
LE
Pisetsky
David S
DS
Haynes
Barton F
BF
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