Profound anti-HIV-1 activity of DAPTA in monocytes/macrophages and inhibition of CCR5-mediated apoptosis in neuronal cells.

Content Provider	Semantic Scholar
Author	Pollicita, Michela Ruff, Michael Pert, Candace B. Polianova, Maria T. Schols, Dominique Ranazzi, Alessandro Perno, Carlo-Federico Aquaro, Stefano
Copyright Year	2007
Abstract	Monocytes/macrophages (M/M) are strategic reservoirs of HIV-1, spreading the virus to other cells and inducing apoptosis in T-lymphocytes, astrocytes and neurons. M/M are commonly infected by R5 HIV-1 strains, which use the chemokine receptor CCR5. D-Ala-peptide T-amide (DAPTA), or Peptide T, named for its high threonine content (ASTTTNYT), is a synthetic peptide comprised of eight amino acids (185-192) of the gp120 V2 region and functions as a viral entry inhibitor by targeting selectively CCR5. The anti-HIV-1 activity of DAPTA was evaluated in M/M infected with R5 HIV-1 strains. DAPTA at 10(-9) M inhibited HIV-1 replication in M/M by > 90%. PCR analysis of viral cDNA in M/M showed that DAPTA blocks HIV entry and in this way prevents HIV-1 infection. Moreover, DAPTA acts as a strong inhibitor and was more active than the non-peptidic CCR5 antagonist TAK-779 in inhibiting apoptosis (mediated by RS HIV-1 strains produced and released by infected M/M) on a neuroblastoma cell line. Our results suggest that antiviral compounds which interfere with receptor mechanisms such as CCR5 could be important, either alone or in combination with other antiretroviral treatments, in preventing HIV infection in the central nervous system and the consequential neuronal damage that leads to neuronal AIDS.
Starting Page	2005
Ending Page	2014
Page Count	10
File Format	PDF HTM / HTML
Alternate Webpage(s)	https://www.intmedpress.com/serveFile.cfm?sUID=3c21be7d-16a4-40d8-98b3-93d08fc49e92
PubMed reference number	18046961v1
Volume Number	18
Issue Number	5
Journal	Antiviral chemistry & chemotherapy
Language	English
Access Restriction	Open
Subject Keyword	Acquired Immunodeficiency Syndrome Amino Acids Antiviral Agents Apoptosis CNS disorder Cultured Cell Line DNA, Complementary HIV Infections Inhibition Name Nerve Degeneration Peptide T R5 human immunodeficiency virus type 1 Reservoir Device Component TAK 779 Threonine cellular targeting chemokine receptor
Content Type	Text
Resource Type	Article