对一名发展为HIV相关痴呆的长期存活者的血液和脑脊液中nef/长末端重复序列缺失的HIV-1进行纵向分析。

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.

作者信息

Churchill Melissa, Sterjovski Jasminka, Gray Lachlan, Cowley Daniel, Chatfield Catherine, Learmont Jennifer, Sullivan John S, Crowe Suzanne M, Mills John, Brew Bruce J, Wesselingh Steven L, McPhee Dale A, Gorry Paul R

机构信息

Macfarlane Burnet Institute for Medical Research and Public Health, Melbourne, Australia.

出版信息

J Infect Dis. 2004 Dec 15;190(12):2181-6. doi: 10.1086/425585. Epub 2004 Nov 16.

DOI:10.1086/425585

PMID:15551218

Abstract

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- kappa B 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.

摘要

我们研究了一名发展为与人类免疫缺陷病毒相关痴呆症（HIVD）的长期存活者体内缺失nef/长末端重复序列（nef/LTR）的1型人类免疫缺陷病毒（HIV-1）的演变和区室化情况。对HIVD发生之前及期间连续分离的血液来源HIV-1进行分析，发现其持续呈现R5X4表型，且nef/LTR序列逐渐缺失；相比之下，HIVD期间脑脊液中存在的HIV-1具有R5表型，其nef/LTR序列有独特的缺失以及额外的核因子κB位点和特异性因子1位点，并且与血液来源的分离株相比，转录活性增强。因此，缺失nef/LTR的HIV-1毒株可能在长期存活者体内经历区室化演变并引发神经疾病。