Immunological response to peptide nucleic acid and its peptide conjugate targeted to transactivation response (TAR) region of HIV-1 RNA genome.
Anti-human immunodeficiency virus-1 (HIV-1) polyamide (peptide) nucleic acids (PNAs) conjugated with cell-penetrating peptides (CPPs) targeted to the viral genome are potent virucidal and antiviral agents. Earlier, we have shown that the anti-HIV-1 PNA(TAR)-penetratin conjugate is rapidly taken up by cells and is nontoxic to mice when administered at repeat doses of as high as 100 mg/kg body weight. In the present studies we demonstrate that naked PNA(TAR) is immunologically inert as judged by the proliferation responses of splenocytes and lymph node cells from PNA(TAR)-immunized mice challenged with the immunizing antigen. In contrast, PNA(TAR)-penetratin conjugate is moderately immunogenic mainly due to its penetratin peptide component. Cytokine secretion profiles of the lymph node cells from the conjugate-immunized mice showed marginally elevated levels of proinflammatory cytokines, which are known to promote proliferation of T lymphocytes. Since the candidate compound, PNA(TAR)-penetratin conjugate displays potent virucidal and antiviral activities against HIV-1, the favorable immunological response together with negligible toxicity suggest a strong therapeutic potential for this class of compounds.
Upadhyay
Alok
A
Department of Biochemistry and Molecular Biology, University of Medicine and Dentistry, New Jersey Medical School, Newark, New Jersey 07103, USA.
Ponzio
Nicholas M
NM
Pandey
Virendra N
VN
D000818:Animals; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000276:immunology*; D002352:Carrier Proteins / Q000008:administration & dosage / Q000276:immunology*; D049109:Cell Proliferation / Q000187:drug effects; D057846:Cell-Penetrating Peptides; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D005260:Female; D005814:Genes, Viral; D016325:HIV Long Terminal Repeat / Q000276:immunology*; D015497:HIV-1 / Q000187:drug effects* / Q000276:immunology; D008198:Lymph Nodes / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D020135:Peptide Nucleic Acids / Q000008:administration & dosage / Q000276:immunology*; D012367:RNA, Viral / Q000235:genetics / Q000276:immunology*; D013154:Spleen / Q000187:drug effects / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D019380:Anti-HIV Agents; D002352:Carrier Proteins; D057846:Cell-Penetrating Peptides; D016207:Cytokines; D020135:Peptide Nucleic Acids; D012367:RNA, Viral; C414409:penetratin