The impact of early immune destruction on the kinetics of postacute viral replication in rhesus monkey infected with the simian-human immunodeficiency virus 89.6P.
Set-point viral load is positively correlated with the extent of initial viral replication in pathogenic simian-human immunodeficiency virus (SHIV) infection. To elucidate the mechanisms underlying the correlation, we conducted a systematic investigation in rhesus monkeys infected with the highly pathogenic SHIV 89.6P. This model is widely used in the preclinical evaluation of AIDS vaccine candidates and a thorough understanding of the model's biology is important to the proper interpretation of these evaluations. We found that the levels of peak viremia were positively correlated not only with the levels of set-point viremia but, importantly, with the extent of initial overall immune destruction as indicated by the degree of CD4+ T cell depletion and lymph node germinal center (GC) formation. The extent of initial overall immune destruction was inversely correlated with subsequent development and maintenance of virus-specific cellular and humoral immune responses. Thus, these data suggest that the extent of early immune damage determines the development and durability of virus-specific immunity, thereby playing a critical role in establishing the levels of set-point viral replication in SHIV infection. Vaccines that limit both the initial viral replication and the extent of early immune damage will therefore mediate long-term virus replication control and mitigation of long-term immune destruction in this model of immunodeficiency virus infection.
Department of Viral Vaccine Research, Merck Research Laboratories, West Point, PA 19486, USA. zhiqiang_zhang@merck.com
Zhi-Qiang
ZQ
Zhang
William A
WA
Schleif
Danilo R
DR
Casimiro
Larry
L
Handt
Minchun
M
Chen
Mary-Ellen
ME
Davies
Xiaoping
X
Liang
Tong-Ming
TM
Fu
Aimin
A
Tang
Keith A
KA
Wilson
Michael
M
McElhaugh
Anthony
A
Carella
Charles
C
Tan
Brett
B
Connolly
Susan
S
Hill
Hilton
H
Klein
Emilio A
EA
Emini
John W
JW
Shiver
D000208:Acute Disease; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D004195:Disease Models, Animal; D018858:Germinal Center / Q000276:immunology; D015497:HIV-1 / Q000235:genetics; D008198:Lymph Nodes / Q000276:immunology / Q000821:virology; D008253:Macaca mulatta; D012367:RNA, Viral / Q000032:analysis; D011995:Recombination, Genetic; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000473:pathology / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000302:isolation & purification / Q000472:pathogenicity* / Q000502:physiology; D013997:Time Factors; D014766:Viremia / Q000276:immunology* / Q000473:pathology; D014779:Virus Replication
D012367:RNA, Viral