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AIDS Weekly Plus
New Gene Therapy Findings from University College London Published
Staff Writer
December 24, 2012


2012 DEC 24 (NewsRx) -- By a News Reporter-Staff News Editor at AIDS Weekly -- Investigators discuss new findings in Biotechnology. According to news reporting out of London, United Kingdom, by NewsRx editors, research stated, "TRIM5 alpha (tripartite motif-containing protein-5, isoform alpha)-cyclophilin A fusion proteins are anti-human immunodeficiency virus (HIV) restriction factors that have evolved in certain nonhuman primates over millions of years and protect against HIV and related viruses. Restriction by TRIM5 alpha CypA is potent and highly resistant to viral escape by mutation and, in combination with a suitable gene delivery platform, offers the possibility of novel therapeutic approaches against HIV."

Our news journalists obtained a quote from the research from University College London, "Here we report that lentiviral vector delivery of human mimics of TRIM5 alpha-cyclophilin A (TRIM5CypA) fusion proteins afforded robust and durable protection against HIV-1, but resulted in downregulation of host cell antiviral responses mediated by endogenous TRIM5 alpha. We found that substitution of TRIM5 alpha RING, B-box, and coiled-coil domains with similar domains from a related TRIM protein, TRIM21, produced a novel and equally potent inhibitor of HIV-1. Both TRIM5CypA and TRIM21CypA inhibited transduction by HIV-1-derived viral vectors and prevented propagation of replication-competent HIV-1 in human cell lines and in primary human T cells. Restriction factor-modified T cells exhibited preferential survival in the presence of wild-type HIV. Restriction was dependent on proteasomal degradation and was reversed in the presence of the cyclophilin inhibitor cyclosporin. Importantly, TRIM21CypA did not disturb endogenous TRIM5 alpha-mediated restriction of gammaretroviral infection. Furthermore, endogenous TRIM21 antiviral activity was assessed by measuring inhibition of adenovirus-antibody complexes and was found to be preserved in all TRIMCypA-modified groups."

According to the news editors, the research concluded: "We conclude that lentivirus-mediated expression of the novel chimeric restriction factor TRIM21CypA provides highly potent protection against HIV-1 without loss of normal innate immune TRIM activity."

For more information on this research see: Lentiviral Gene Therapy Against Human Immunodeficiency Virus Type 1, Using a Novel Human TRIM21-Cyclophilin A Restriction Factor. Human Gene Therapy, 2012;23(11):1176-1185. Human Gene Therapy can be contacted at: Mary Ann Liebert Inc, 140 Huguenot Street, 3RD Fl, New Rochelle, NY 10801, USA. (Mary Ann Liebert, Inc. - www.liebertpub.com; Human Gene Therapy - www.liebertpub.com/overview/human-gene-therapy-and-part-b-methods/19/)

Our news journalists report that additional information may be obtained by contacting E. Chan, UCL, Div Infect & Immun, London W1T 4JF, United Kingdom (see also Biotechnology).

Keywords for this news article include: Biotechnology, London, Europe, Genetics, HIV/AIDS, Virology, Immunology, RNA Viruses, Cyclophilins, Gene Therapy, Retroviridae, Immunophilins, United Kingdom, HIV Infections, Membrane Proteins, Vertebrate Viruses, Primate Lentiviruses, cis-trans-Isomerases, Enzymes and Coenzymes, Human Immunodeficiency Virus

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