Gp120 sequence variation in brain and in T-lymphocyte human immunodeficiency virus type 1 primary isolates

Objective: We sought to identify genetic determinants within human immunodeficiency virus type 1 (HIV-1) gp120 that differentiate viral species in brain from those in lymphocytes. Study Design/Methods: Polymerase chain reaction (PCR) was used to amplify gp120 genes from paired brain and T-cell isolates from two infants and two adults with dementia. Amplimers were molecularly cloned and sequenced. Results: The degrees of amino acid divergence between brain and T-cell clones for the two adults were 7.7% and 8.6% and, for the two infants, 2.4% and 2.7%. For one adult and one infant, divergence was greater among brain cell clones than T-cell clones. In the adults, a 3-amino acid insertion, located similarly within V4 and encoding asparagine residues, was identified in the T-cell clones. Conclusions: HIV-1 genetic variation within brain cells is not necessarily restricted compared with that in blood lymphocytes. The species in brain cells can be distinguished from those in lymphocytes by determinants within V4. These differences suggest that immune-mediated selection ongoing within lymphoid cell compartments may not occur within brain.