Longitudinal analysis of nef/long terminal repeat-deleted HIV-1 in blood and cerebrospinal fluid of a long-term survivor who developed HIV-associated dementia

被引:25
作者
Churchill, M
Sterjovski, J
Gray, L
Cowley, D
Chatfield, C
Learmont, J
Sullivan, JS
Crowe, SM
Mills, J
Brew, BJ
Wesselingh, SL
McPhee, DA
Gorry, PR
机构
[1] Macfarlane Burnet Inst Med Res & Publ Hlth, Melbourne, Vic 3001, Australia
[2] Monash Univ, Dept Med, Melbourne, Vic 3004, Australia
[3] Univ Melbourne, Dept Microbiol & Immunol, Parkville, Vic 3052, Australia
[4] Univ Sydney, Australian Red Cross Blood Serv, Sydney, NSW, Australia
[5] Univ Sydney, Fac Med, Sydney, NSW, Australia
[6] St Vincents Hosp, Darlinghurst, NSW 2010, Australia
基金
英国医学研究理事会; 美国国家卫生研究院;
关键词
D O I
10.1086/425585
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
We studied the evolution and compartmentalization of nef/ long terminal repeat ( nef/ LTR) - deleted human immunodeficiency virus type 1 (HIV-1) from a long-term survivor who developed HIV-associated dementia (HIVD). Analysis of sequential blood-derived HIV-1 isolated before and during HIVD revealed a persistent R5X4 phenotype and a progressive loss of nef/ LTR sequence; in contrast, HIV-1 present in cerebrospinal fluid during HIVD had an R5 phenotype, distinct nef/ LTR sequence of unique deletions and additional nuclear factor - kappaB sites and specificity factor - 1 sites, and enhanced transcriptional activity, compared with the blood-derived isolates. Thus, nef/LTR-deleted HIV-1 strains may undergo compartmentalized evolution in long-term survivors and cause neurologic disease.
引用
收藏
页码:2181 / 2186
页数:6
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