title: Mamu-A*01 allele-mediated attenuation of disease progression in simian-human immunodeficiency virus infection.
abstract: 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.
authors.affiliation: 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
authors.forename: Zhi-Qiang
authors.initials: ZQ
authors.lastname: Zhang
authors.forename: Tong-Ming
authors.initials: TM
authors.lastname: Fu
authors.forename: Danilo R
authors.initials: DR
authors.lastname: Casimiro
authors.forename: Mary-Ellen
authors.initials: ME
authors.lastname: Davies
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Liang
authors.forename: William A
authors.initials: WA
authors.lastname: Schleif
authors.forename: Larry
authors.initials: L
authors.lastname: Handt
authors.forename: Lynda
authors.initials: L
authors.lastname: Tussey
authors.forename: Minchun
authors.initials: M
authors.lastname: Chen
authors.forename: Aimin
authors.initials: A
authors.lastname: Tang
authors.forename: Keith A
authors.initials: KA
authors.lastname: Wilson
authors.forename: Wendy L
authors.initials: WL
authors.lastname: Trigona
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Freed
authors.forename: Charles Y
authors.initials: CY
authors.lastname: Tan
authors.forename: Melanie
authors.initials: M
authors.lastname: Horton
authors.forename: Emilio A
authors.initials: EA
authors.lastname: Emini
authors.forename: John W
authors.initials: JW
authors.lastname: Shiver
mesh_terms: 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
chemical_list: D016915:AIDS Vaccines; D015683:Gene Products, gag; D015395:Histocompatibility Antigens Class I; C110764:Mamu-A 01 antigen