TY - JOUR
T1 - Profound anti-HIV-1 activity of DAPTA in monocytes/macrophages and inhibition of CCR5-mediated apoptosis in neuronal cells
AU - Pollicita, Michela
AU - Ruff, Michael R.
AU - Pert, Candace B.
AU - Polianova, Maria T.
AU - Schols, Dominique
AU - Ranazzi, Alessandro
AU - Perno, Carlo Federico
AU - Aquaro, Stefano
PY - 2007
Y1 - 2007
N2 - 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 10-9M 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 R5 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.
AB - 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 10-9M 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 R5 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.
KW - Apoptosis
KW - CCR5
KW - Entry inhibitors
KW - HIV-1
KW - Monocytes/macrophages
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M3 - Article
C2 - 18046961
AN - SCOPUS:36849030737
VL - 18
SP - 285
EP - 295
JO - Antiviral Chemistry and Chemotherapy
JF - Antiviral Chemistry and Chemotherapy
SN - 0956-3202
IS - 5
ER -