Correlation of naturally occurring HIV-1 resistance to DEB025 with capsid amino acid polymorphisms.
Correlation of naturally occurring HIV-1 resistance to DEB025 with capsid amino acid polymorphisms.
复制标题
DOI：
10.3390/v5030981
复制
发表时间：
2013-03-22
期刊：
影响因子：
--
通讯作者：
Rosenwirth B
中科院分区：
文献类型：
--
作者：
Gallay PA;Ptak RG;Bobardt MD;Dumont JM;Vuagniaux G;Rosenwirth B
DEB025 (alisporivir) is a synthetic cyclosporine with inhibitory activity against human immunodeficiency virus type-1 (HIV-1) and hepatitis C virus (HCV). It binds to cyclophilin A (CypA) and blocks essential functions of CypA in the viral replication cycles of both viruses. DEB025 inhibits clinical HIV-1 isolates in vitro and decreases HIV-1 virus load in the majority of patients. HIV-1 isolates being naturally resistant to DEB025 have been detected in vitro and in nonresponder patients. By sequence analysis of their capsid protein (CA) region, two amino acid polymorphisms that correlated with DEB025 resistance were identified: H87Q and I91N, both located in the CypA-binding loop of the CA protein of HIV-1. The H87Q change was by far more abundant than I91N. Additional polymorphisms in the CypA-binding loop (positions 86, 91 and 96), as well as in the N-terminal loop of CA were detected in resistant isolates and are assumed to contribute to the degree of resistance. These amino acid changes may modulate the conformation of the CypA-binding loop of CA in such a way that binding and/or isomerase function of CypA are no longer necessary for virus replication. The resistant HIV-1 isolates thus are CypA-independent.
登录
查看更多内容
影响因子：
3.7
作者：
Coelmont L;Hanoulle X;Chatterji U;Berger C;Snoeck J;Bobardt M;Lim P;Vliegen I;Paeshuyse J;Vuagniaux G;Vandamme AM;Bartenschlager R;Gallay P;Lippens G;Neyts J
通讯作者：
Neyts J
影响因子：
5.4
作者：
Braaten, D;Franke, EK;Luban, J
通讯作者：
Luban, J
影响因子：
4.8
作者：
Chatterji, Udayan;Bobardt, Michael D.;Gallay, Philippe A.
通讯作者：
Gallay, Philippe A.
DOI：
10.1073/pnas.0505659102
发表时间：
2005-10-11
影响因子：
11.1
作者：
Berthoux, L;Sebastian, S;Luban, J
通讯作者：
Luban, J
影响因子：
13.5
作者：
Flisiak, Robert;Horban, Andrzej;Scalfaro, Pietro
通讯作者：
Scalfaro, Pietro