Abstract:
:Human immunodeficiency virus type 1 (HIV-1) sequences were generated from blood and from brain tissue obtained by stereotactic biopsy from six patients undergoing a diagnostic neurosurgical procedure. Proviral DNA was directly amplified by nested PCR, and 8 to 36 clones from each sample were sequenced. Phylogenetic analysis of intrapatient envelope V3-V5 region HIV-1 DNA sequence sets revealed that brain viral sequences were clustered relative to the blood viral sequences, suggestive of tissue-specific compartmentalization of the virus in four of the six cases. In the other two cases, the blood and brain virus sequences were intermingled in the phylogenetic analyses, suggesting trafficking of virus between the two tissues. Slide-based PCR-driven in situ hybridization of two of the patients' brain biopsy samples confirmed our interpretation of the intrapatient phylogenetic analyses. Interpatient V3 region brain-derived sequence distances were significantly less than blood-derived sequence distances. Relative to the tip of the loop, the set of brain-derived viral sequences had a tendency towards negative or neutral charge compared with the set of blood-derived viral sequences. Entropy calculations were used as a measure of the variability at each position in alignments of blood and brain viral sequences. A relatively conserved set of positions were found, with a significantly lower entropy in the brain-than in the blood-derived viral sequences. These sites constitute a brain "signature pattern," or a noncontiguous set of amino acids in the V3 region conserved in viral sequences derived from brain tissue. This brain-derived signature pattern was also well preserved among isolates previously characterized in vitro as macrophage tropic. Macrophage-monocyte tropism may be the biological constraint that results in the conservation of the viral brain signature pattern.
journal_name
J Viroljournal_title
Journal of virologyauthors
Korber BT,Kunstman KJ,Patterson BK,Furtado M,McEvilly MM,Levy R,Wolinsky SMdoi
10.1128/JVI.68.11.7467-7481.1994subject
Has Abstractpub_date
1994-11-01 00:00:00pages
7467-81issue
11eissn
0022-538Xissn
1098-5514journal_volume
68pub_type
杂志文章abstract::The C-terminal domain of human immunodeficiency virus type 1 (HIV-1) integrase (IN) is a dimer that binds to DNA in a nonspecific manner. The structure of the minimal region required for DNA binding (IN220-270) has been solved by nuclear magnetic resonance spectroscopy. The overall fold of the C-terminal domain of HIV...
journal_title:Journal of virology
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pub_type: 杂志文章
doi:10.1128/JVI.70.12.8310-8317.1996
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doi:10.1128/JVI.70.12.8727-8736.1996
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.53.2.462-468.1985
更新日期:1985-02-01 00:00:00
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pub_type: 杂志文章
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.62.5.1753-1761.1988
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pub_type: 杂志文章
doi:10.1128/JVI.73.1.738-745.1999
更新日期:1999-01-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00362-14
更新日期:2014-06-01 00:00:00
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pub_type: 杂志文章
doi:10.1128/JVI.59.1.120-126.1986
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doi:10.1128/JVI.12.4.721-732.1973
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.63.5.2411-2414.1989
更新日期:1989-05-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.12.1.49-57.1973
更新日期:1973-07-01 00:00:00
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pub_type: 杂志文章
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更新日期:2006-09-01 00:00:00
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pub_type: 杂志文章
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pub_type: 杂志文章
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pub_type: 杂志文章
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.61.12.3832-3840.1987
更新日期:1987-12-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.70.9.6151-6156.1996
更新日期:1996-09-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.70.12.8813-8820.1996
更新日期:1996-12-01 00:00:00