Frequency of HLA allele-specific peptide motifs in HIV-1 proteins correlates with the allele's association with relative rates of disease progression after HIV-1 infection.
Frequency of HLA allele-specific peptide motifs in HIV-1 proteins correlates with the allele's association with relative rates of disease progression after HIV-1 infection.
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HIV-1 蛋白中 HLA 等位基因特异性肽基序的频率与等位基因与 HIV-1 感染后疾病进展的相对速率相关。
DOI：
10.1073/pnas.94.18.9802
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发表时间：
1997
影响因子：
11.1
通讯作者：
D. Mann
中科院分区：
文献类型：
--
作者：
G. Nelson;R. Kaslow;D. Mann
HLA 等位基因特异性细胞毒性 T 淋巴细胞反应被认为会影响 HIV-1 感染者的疾病进展速度。在之前对 139 名感染 HIV-1 的同性恋男性进行的研究中，我们鉴定了 HLA I 类等位基因，并观察到特定等位基因与进展为 AIDS 的不同相对风险之间的关联。为了寻求这种关联的解释，我们搜索了 HIV-1 蛋白质序列，以确定与据报道结合 16 个 I 类等位基因的特定氨基酸组合定义的基序相匹配的肽的数量。通过分析 12 个 B 分支 HIV 分离株的完整序列，我们确定了保守（在所有 12 个分离株中出现）和非保守（仅在一个分离株中出现）的等位基因基序的数量，以及每个分离株的平均等位基因基序数。我们发现，gag（R = 0.73；P = 0.002）、pol（R = 0.58，P = 0.024）、gp120（R = 0.78，P = 0.00056）和总病毒蛋白序列（R = 0.67，P = 0.0058）中保守基序的计数与等位基因与疾病进展的关联存在显着相关性。还用于 gag (R = 0.62，P = 0.013)、pol (R = 0.74，P = 0.0017)、gp41 (R = 0.52，P = 0.046) 和总病毒蛋白 (R = 0.71，P = 0.0033) 中非保守基序的计数。我们还发现每个分离株的 gag、pol、gp120 和总病毒蛋白的平均基序数存在显着相关性。这项研究为观察到的不同 HLA 等位基因与不同疾病进展率之间的关联提供了合理的功能解释。
An HLA allele-specific cytotoxic T lymphocyte response is thought to influence the rate of disease progression in HIV-1-infected individuals. In a prior study of 139 HIV-1-infected homosexual men, we identified HLA class I alleles and observed an association of specific alleles with different relative hazards for progression to AIDS. Seeking an explanation for this association, we searched HIV-1 protein sequences to determine the number of peptides matching motifs defined by combinations of specific amino acids reported to bind 16 class I alleles. Analyzing complete sequences of 12 clade B HIV isolates, we determined the number of allele motifs that were conserved (occurring in all 12 isolates) and nonconserved (occurring in only one isolate), as well as the average number of allele motifs per isolate. We found significant correlations with an allele's association with disease progression for counts of conserved motifs in gag (R = 0.73; P = 0.002), pol (R = 0.58, P = 0.024), gp120 (R = 0.78, P = 0.00056), and total viral protein sequences (R = 0.67, P = 0.0058) and also for counts of nonconserved motifs in gag (R = 0.62, P = 0.013), pol (R = 0.74, P = 0.0017), gp41 (R = 0.52, P = 0.046), and total viral protein (R = 0.71, P = 0.0033). We also found significant correlations for the average number of motifs per isolate for gag, pol, gp120, and total viral protein. This study provides a plausible functional explanation for the observed association of different HLA alleles with variable rates of disease progression.
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HIV-1 gag 特异性细胞毒性 T 淋巴细胞识别多个高度保守的表位。
DOI：
--
发表时间：
1991
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Johnson,RP;Trocha,A;Yang,L;Mazzara,GP;Panicali,DL;Buchanan,TM;Walker,BD
通讯作者：
Walker,BD
从病毒基因组的保守区域鉴定 A2 限制性丙型肝炎病毒特异性细胞毒性 T 淋巴细胞表位。
影响因子：
4.4
作者：
Wentworth,PA;Sette,A;Celis,E;Sidney,J;Southwood,S;Crimi,C;Stitely,S;Keogh,E;Wong,NC;Livingston,B;Alazard,D;Vitiello,A;Grey,HM;Chisari,FV;Chesnut,RW;Fikes,J
通讯作者：
Fikes,J
影响因子：
4.4
作者：
Ralph T. Kubo;Alessandro Sette;Howard M. Grey;Ettore Appella;Kazuyasu Sakaguchi;N. Zhu;D. Arnott;Nicholas E. Sherman;J. Shabanowitz;Hanspeter Michel
通讯作者：
Ralph T. Kubo;Alessandro Sette;Howard M. Grey;Ettore Appella;Kazuyasu Sakaguchi;N. Zhu;D. Arnott;Nicholas E. Sherman;J. Shabanowitz;Hanspeter Michel
影响因子：
4.4
作者：
J. Sidney;M. D. Guercio;S. Southwood;V. Engelhard;E. Appella;H. Rammensee;K. Falk;O. Rötzschke;M. Takiguchi;R. Kubo
通讯作者：
J. Sidney;M. D. Guercio;S. Southwood;V. Engelhard;E. Appella;H. Rammensee;K. Falk;O. Rötzschke;M. Takiguchi;R. Kubo
影响因子：
32.4
作者：
TUSSEY, LG;ROWLANDJONES, S;MCMICHAEL, AJ
通讯作者：
MCMICHAEL, AJ