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183 HIV Exposes Major “Trafficking” in HERV- K HML-2 Viruses Which are Critical to the Pathogenesis of HIV Infection and Lymphoma

Kaplan, M H; Contreras-Galindo, R; Gonzalez-Hernandez, M; Gitlin, S D; Dosik, M H; Markovitz, D

JAIDS Journal of Acquired Immune Deficiency Syndromes: April 2011 - Volume 56 - Issue - p 76
doi: 10.1097/01.qai.0000397365.84039.ce
Abstracts
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Dept. Medicine, University of Michigan, Ann Arbor MI

We have shown that in HIV Infection the human endogenous retrovirus- K (HML-2) (HERV K) is found in the plasma of patients(Pts) with HIV and HIV associated lymphoma (HIV-L) to concentrations as high as 1010. HERV K virions can be seen in plasma by immunoelectron microscopy, detected by gagRT-PCR and can demonstrate reverse transcriptase activity in the appropriate viral density using iodoxanol gradients. Similar high titer HERV K is found in non-HIVassociated Lymphoma (nonHIV-L). Using primers for RT-PCR which span >1000bp of the HERV K type 1 and type2 env and then cloning and sequencing amplicons, we detect different HERV K species in plasma of HIV, HIVL and non HIVL Pts. We constructed neighbor joining phylogenetic trees (MEGA) (PhyTs) to relate these to the known HERV K species defined in the NCBI and the HERVd data bases. We found 15/171 different Type-1 and 18/115 different Type-2 HERV-K (HML-2) cloned sequence in HIV patients. Viruses demonstrated frequent recombination between Type1/Type1 and Type 1/Type2 HERV K. A unique new HERV K type 1 virus called K111 was discovered as a multicopy polyprovirus. PhyTs were similarly constructed from plasma samples taken serially years before and up to the development of HIV L. Pts showed increasing HERV K viral loads prior to HIV L. Multiple HERV Ks appeared with high rates of recombination. Several new viruses with unresolved topologies appear in HIV L. Patients with HIV Diffuse Large B cell (DLBL) lymphoma show a different HERV K pattern than those with HIV Burkitt's lymphoma (BL). PhyTs are now being constructed from patients with non HIV L. HERV K Rec Antibodies are also elevated in lymphomas. HERV K HML-2 viruses are actively being trafficked in blood in HIV and nonHIV L providing new insights to the pathogenesis of lymphoma.

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