Mamu-A*01 allele-mediated attenuation of disease progression in simian-human immunodeficiency virus infection.
Expression of several major histocompatibility complex (MHC) class I alleles is associated with a protective effect against disease progression in both human immunodeficiency virus type 1 and simian immunodeficiency virus infection. To understand the mechanism underlying this effect, we investigated the expression of the MHC class I allele Mamu-A*01 in simian-human immunodeficiency virus (SHIV) infection, one of the major models for evaluation of AIDS vaccine candidates. We found that disease progression was significantly delayed in Mamu-A*01-positive rhesus monkeys infected with the highly pathogenic SHIV 89.6P. The delay corresponded not only to a noted Mamu-A*01-restricted dominant cytotoxic T-lymphocyte (CTL) response but also to a lower viral load in lymph nodes (LN) and, importantly, to minimal destruction of LN structure during early infection. In contrast, Mamu-A*01-negative monkeys exhibited massive destruction of LN structure with accompanying rapid disease progression. These data indicate that MHC class I allele-restricted CTL responses may play an important role in preservation of lymphoid tissue structure, thereby resulting in attenuation of disease progression in immunodeficiency virus infection.
Zhang
Zhi-Qiang
ZQ
Department of Viral Vaccine Research, Merck Research Laboratories, 770 Sumneytown Pike, PO Box 4, WP16-225, West Point, PA 19486, USA. zhiqiang_zhang@merck.com
Fu
Tong-Ming
TM
Casimiro
Danilo R
DR
Davies
Mary-Ellen
ME
Liang
Xiaoping
X
Schleif
William A
WA
Handt
Larry
L
Tussey
Lynda
L
Chen
Minchun
M
Tang
Aimin
A
Wilson
Keith A
KA
Trigona
Wendy L
WL
Freed
Daniel C
DC
Tan
Charles Y
CY
Horton
Melanie
M
Emini
Emilio A
EA
Shiver
John W
JW
D016915:AIDS Vaccines / Q000276:immunology; D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology*; D000483:Alleles; D000818:Animals; D018791:CD4 Lymphocyte Count; D020566:Dendritic Cells, Follicular / Q000473:pathology; D018450:Disease Progression; D015683:Gene Products, gag / Q000032:analysis; D005805:Genes, MHC Class I / Q000502:physiology*; D018858:Germinal Center / Q000473:pathology; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D008198:Lymph Nodes / Q000821:virology; D008253:Macaca mulatta; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology*; D019562:Viral Load
D016915:AIDS Vaccines; D015683:Gene Products, gag; D015395:Histocompatibility Antigens Class I; C110764:Mamu-A 01 antigen