AEGiS-15IAC: Restricted HIV genomic variability in AIDS dementia and lymphoma.

15th International AIDS Conference

Bangkok, Thailand - July 11-16, 2004

Restricted HIV genomic variability in AIDS dementia and lymphoma.

Int Conf AIDS 2004 Jul 11-16; 15:(abstract no. ThOrA1399)

McGrath MS, Yu S, Jin X, Reis J, Lamers S
University of California, San Francisco, San Francisco, United States

BACKGROUND: Viral reservoirs, such as the brain, signify a major obstacle in eradicating HIV infection. The evolution of HIV-1 in the brain is distinct from that in other lymphoid tissues in that brain-derived viruses are always macrophage (MO) tropic and primarily use the CCR5 co-receptor for virus entry. These viruses are likely to contribute to long-term persistence of infection. HIV-1 envelope sequences display less genetic variation in macrophage (MO)-associated tissues than in T-cell-associated tissues. Various studies have examined compartmentalization of HIV-1 in a variety of tissues; however, no published study describes HIV-1 genetic variation within HIV-induced tumors. In this preliminary study, we compared genetic variability within tissues from several body compartments including brain and lymphoma.

METHODS: DNA was extracted from frozen tissues and HIV V3 region env specific primers were used for PCR amplification and cloning. HIVbase ó ä ó software was used to process genetic data. Several methods were employed (phylogeny, intra- and inter-sample variation, alignments) to analyze 20+ clones from each of 3 lymphoma (HIV+ MO's), 5 brain and a variety of control tissue samples (from ACSR, url: http://acsr.ucsf.edu).

RESULTS: Distance analysis revealed restricted internal variation within lymphoma and brain clones as compared to control tissues, which showed rates of intrasample variation of up to 7.9%. Additionally, using several different types of phylogeny methods, lymphoma and brain sequences often formed monophyletic clades, distinct from control sequences. V3 loop env sequences in brain and lymphoma displayed charges of +2 to +4.

CONCLUSIONS: The observation of reduced HIV genetic variation and low V3 loop charges in both brain and lymphoma suggest the expansion of macrophages rather than blood-brain barrier restricted HIV replication. These findings also suggest that a subset of lymphomas contain clonally restricted MO associated HIV that can serve as a viral reservoir and may contribute to lymphomagenesis.

Keywords: AEGIS, AIDS Dementia Complex, HIV, Acquired Immunodeficiency Syndrome, HIV Seropositivity, HIV-1, HIV Infections, Receptors, CCR5, Genes, env, HIV Envelope Protein gp120, Brain, Receptors, HIV, Virus Replication, Lymphoma, Macrophages, HIV Seronegativity, Phylogeny, Polymerase Chain Reaction, Lymphoid Tissue, Variation (Genetics), genetics, immunology, virology

040711
ThOrA1399