Transmission of HIV-1 Gag immune escape mutations is associated with reduced viral load in linked recipients.
Transmission of HIV-1 Gag immune escape mutations is associated with reduced viral load in linked recipients.
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DOI：
10.1084/jem.20072457
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发表时间：
2008-05-12
期刊：
影响因子：
--
通讯作者：
Hunter E
中科院分区：
文献类型：
--
作者：
Goepfert PA;Lumm W;Farmer P;Matthews P;Prendergast A;Carlson JM;Derdeyn CA;Tang J;Kaslow RA;Bansal A;Yusim K;Heckerman D;Mulenga J;Allen S;Goulder PJ;Hunter E
在114流行病学关联的赞比亚传播对的研究中，我们评估了人类白细胞抗原I类（HLA-I）相关的氨基酸多态性的影响，推测反映细胞毒性T淋巴细胞（CTL）逃逸Gag和Nef的病毒从慢性感染的捐助者，在匹配的受体感染后6个月的血浆病毒载量（VL）。在供体中观察到Gag和Nef中的CTL逃逸突变，这些突变随后传播给受体，在感染后不久基本上没有变化。我们观察到受者中特异性HLA-B等位基因限制性CTL靶向的Gag逃逸突变数量与VL减少之间存在显著相关性。这种负相关在新感染的个体中最为明显，其HLA等位基因不能有效靶向Gag并选择该基因中的CTL逃逸突变。供体中的Nef突变对受体中的VL没有影响。因此，能够驱动供体中病毒逃逸的广泛的GAG特异性CTL应答可能对供体和受体都具有临床益处。除了对HIV-1疫苗设计的直接影响外，这些数据还表明CTL诱导的病毒多态性及其相关的体内病毒适应性成本可能对HIV-1发病机制产生重大影响。
In a study of 114 epidemiologically linked Zambian transmission pairs, we evaluated the impact of human leukocyte antigen class I (HLA-I)–associated amino acid polymorphisms, presumed to reflect cytotoxic T lymphocyte (CTL) escape in Gag and Nef of the virus transmitted from the chronically infected donor, on the plasma viral load (VL) in matched recipients 6 mo after infection. CTL escape mutations in Gag and Nef were seen in the donors, which were subsequently transmitted to recipients, largely unchanged soon after infection. We observed a significant correlation between the number of Gag escape mutations targeted by specific HLA-B allele–restricted CTLs and reduced VLs in the recipients. This negative correlation was most evident in newly infected individuals, whose HLA alleles were unable to effectively target Gag and select for CTL escape mutations in this gene. Nef mutations in the donor had no impact on VL in the recipient. Thus, broad Gag-specific CTL responses capable of driving virus escape in the donor may be of clinical benefit to both the donor and recipient. In addition to their direct implications for HIV-1 vaccine design, these data suggest that CTL-induced viral polymorphisms and their associated in vivo viral fitness costs could have a significant impact on HIV-1 pathogenesis.
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CTL逃生变体的传播和积累驱动HIV多态性与HLA之间的负相关。
影响因子：
15.3
作者：
Leslie, A;Kavanagh, D;Honeyborne, I;Pfafferott, K;Edwards, C;Pillay, T;Hilton, L;Thobakgale, C;Ramduth, D;Draenert, R;Le Gall, S;Luzzi, G;Edwards, A;Brander, C;Sewell, AK;Moore, S;Mullins, J;Moore, C;Mallal, S;Bhardwaj, N;Yusim, K;Phillips, R;Klenerman, P;Korber, B;Kiepiela, P;Walker, B;Goulder, P
通讯作者：
Goulder, P
影响因子：
6.7
作者：
Brumme ZL;Brumme CJ;Heckerman D;Korber BT;Daniels M;Carlson J;Kadie C;Bhattacharya T;Chui C;Szinger J;Mo T;Hogg RS;Montaner JS;Frahm N;Brander C;Walker BD;Harrigan PR
通讯作者：
Harrigan PR
DOI：
10.1084/jem.20070784
发表时间：
2007-10-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Almeida JR;Price DA;Papagno L;Arkoub ZA;Sauce D;Bornstein E;Asher TE;Samri A;Schnuriger A;Theodorou I;Costagliola D;Rouzioux C;Agut H;Marcelin AG;Douek D;Autran B;Appay V
通讯作者：
Appay V
影响因子：
5.4
作者：
Brockman, Mark A.;Schneidewind, Arne;Allen, Todd M.
通讯作者：
Allen, Todd M.
影响因子：
2.7
作者：
Johnson, DR
通讯作者：
Johnson, DR