Mamu-A*01 allele-mediated attenuation of disease progression in simian-human immunodeficiency virus infection
| Autor: | Aimin Tang, Danilo R. Casimiro, Zhiqiang Zhang, Lynda Tussey, Larry Handt, Keith A. Wilson, Minchun Chen, William A. Schleif, Emilio A. Emini, Charles Tan, John W. Shiver, Xiaoping Liang, Tong-Ming Fu, Wendy L. Trigona, Melanie Horton, Mary-Ellen Davies, Daniel C. Freed |
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| Rok vydání: | 2002 |
| Předmět: |
animal diseases
Immunology Simian Acquired Immunodeficiency Syndrome Gene Products gag Genes MHC Class I Major histocompatibility complex medicine.disease_cause Microbiology Virus Pathogenesis Virology medicine Animals Allele Alleles AIDS Vaccines Acquired Immunodeficiency Syndrome biology Histocompatibility Antigens Class I virus diseases Simian immunodeficiency virus Viral Load Germinal Center Macaca mulatta CD4 Lymphocyte Count CTL Viral replication Insect Science biology.protein Disease Progression Pathogenesis and Immunity Lymph Nodes Viral load Dendritic Cells Follicular |
| Zdroj: | Journal of virology. 76(24) |
| ISSN: | 0022-538X |
| Popis: | Numerous observations have shown that host genetic factors play important roles in disease progression in human immunodeficiency virus type 1 (HIV-1) infection (24, 28). The genetics of the major histocompatibility complex (MHC) appears to be a particularly critical factor (5). Rapid disease progression has been demonstrated to be associated with certain class I HLA molecules, such as the HLA-B35-Cw∗04 haplotype (3, 11). Slow disease progression is linked with several class I HLA molecules, notably HLA-B∗27 and HLA-B∗57 (13, 17, 23). Recently, this protective effect was demonstrated in a mother-to-child HIV-1 transmission setting, where it was found that HLA-B∗27-restricted immunodominant cytotoxic T-lymphocyte (CTL) responses play a crucial role in delaying disease progression (12). Similar protective effects were also observed in simian immunodeficiency virus (SIV) infection, particularly in association with expression of the Mamu-A∗01 MHC allele. For instance, expression of Mamu-A∗01 significantly delayed disease progression in SIVmac 251 infection (8, 9, 25). Since this allele has been consistently associated with the CTL response to an immunodominant epitope derived from the SIV Gag region (SIV Gag residues 181 to 189, designated p11CM), detectable by sensitive tetramer and ELISPOT assays, Mamu-A∗01 monkeys have been favored for evaluation of AIDS vaccine candidates (1, 2, 29). Infection with a pathogenic isolate of simian-human immunodeficiency virus (SHIV 89.6P), causes severe CD4 lymphopenia and rapid disease progression in rhesus monkeys (16, 27). Because of the highly pathogenic nature of this virus and its consistent replication kinetics in rhesus monkeys, this challenge model is widely adopted for evaluation of potential AIDS vaccines (1, 2, 29). To further understand the pathogenesis of SHIV 89.6P infection, particularly the impact of expression of the Mamu-A∗01 allele on disease progression, we monitored a cohort of intravenously infected rhesus monkeys with and without expression of the Mamu-A∗01 allele. Here we report that expression of the Mamu-A∗01 allele was associated with delayed disease progression to AIDS in SHIV 89.6P infection. Early virus-specific CTL responses, especially Mamu-A∗01-restricted CTL responses, likely contributed to the significant reduction of initial viral replication observed in lymphoid tissue. Reduced viral replication in lymphoid tissue allowed lymphoid tissue structure to remain relatively intact, thereby resulting in attenuation of disease progression. |
| Databáze: | OpenAIRE |
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