S Tehranchi | PubMed Health

PubMed1996

Sequence analysis of the V3 loop in brain and spleen of patients with HIV encephalitis.

Infection with a particularly neurovirulent strain of HIV has been hypothesized to explain why only a subset of patients develops HIV encephalitis. We studied the third hypervariable region (V3) of multiple clones from both brains and spleens of three patients who died with HIV encephalitis, to see if there was a molecular signature associated with neurological disease. Clones from the spleen and brain of individual patients showed significant nucleic acid homology and had envelope sequences characteristic of macrophage-tropic viruses. No brain-specific unique sequences were observed, suggesting that while CNS virus is macrophage tropic there is no evidence in the V3 envelope region studied to suggest a specific neurotropic variant.

Acquired Immunodeficiency Syndrome↗

PubMed1995

Coding end processing is similar throughout ontogeny.

During the recombination process, extensive processing of the coding ends provides tremendous potential diversity to the joint of any two gene segments. However, the diversity of the newborn B and T cell repertoires is greatly reduced compared with that of the adult. At the mechanistic level, this difference is primarily due to the absence of terminal deoxynucleotidyltransferase expression until the first week after birth. Additionally, one direct consequence of the lack of N regions early in ontogeny is the more frequent occurrence of homology-directed recombination, reducing even further the potential of diversity. Other enzymatic factors could also contribute to this ontogenic difference. However, the use of the homology-directed recombination pathway early in life obscures the analysis of the coding end processing. In this study we compared the coding end processing throughout ontogeny, in normal and terminal deoxynucleotidyltransferase -/- mice in the presence of minimal homology-directed recombination. The analysis of partial D-J joints allowed us to avoid potential bias by early selection events. Our results show that the extent of nucleotide deletion of a given end is consistent throughout ontogeny in the presence or absence of terminal deoxynucleotidyltransferase. However, a distinctive processing pattern is observed for each coding end.

Age Factors↗