Vaccination with tat toxoid attenuates disease in simian/HIV-challenged macaques.
The Tat protein is essential for HIV type 1 (HIV-1) replication and may be an important virulence factor in vivo. We studied the role of Tat in viral pathogenesis by immunizing rhesus macaques with chemically inactivated Tat toxoid and challenging these animals by intrarectal inoculation with the simian/human immunodeficiency virus 89.6PD. Immune animals had significantly attenuated disease with lowered viral RNA, interferon-alpha, and chemokine receptor expression (CXCR4 and CCR5) on CD4(+) T cells; these features of infection have been linked to in vitro effects of Tat and respond similarly to extracellular Tat protein produced during infection. Immunization with Tat toxoid inhibits key steps in viral pathogenesis and should be included in therapeutic or preventive HIV-1 vaccines.
Pauza
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CD
Department of Pathology and Laboratory Medicine, University of Wisconsin and Wisconsin Regional Primate Research Center, Madison, WI 53706, USA. cdpauza@facstaff.wisc.edu
Trivedi
P
P
Wallace
M
M
Ruckwardt
T J
TJ
Le Buanec
H
H
Lu
W
W
Bizzini
B
B
Burny
A
A
Zagury
D
D
Gallo
R C
RC
D000818:Animals; D018791:CD4 Lymphocyte Count; D002678:Chimera; D005434:Flow Cytometry; D015696:Gene Products, tat / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D008253:Macaca mulatta; D012367:RNA, Viral / Q000097:blood; D019713:Receptors, CCR5 / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000378:metabolism; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D019562:Viral Load; D014779:Virus Replication; D054322:tat Gene Products, Human Immunodeficiency Virus
D015696:Gene Products, tat; D012367:RNA, Viral; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D054322:tat Gene Products, Human Immunodeficiency Virus