Novel anti-HIV-1 activity produced by conjugating unsulfated dextran with polyl-lysine

• Published in: Antiviral research Vol. 94; no. 1; pp. 89 - 97
• Main Authors: Nakamura, Kosuke, Ohtsuki, Takahiro, Mori, Haruyo, Hoshino, Hiroo, Hoque, Ariful, Oue, Atsushi, Kano, Fumie, Sakagami, Hiromi, Tanamoto, Ken-ichi, Ushijima, Hiroshi, Kawasaki, Nana, Akiyama, Hiroshi, Ogawa, Haruko
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier B.V 01.04.2012; Elsevier
• Subjects: Animals; Anti-HIV Agents - chemistry; Anti-HIV Agents - pharmacology; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Biological and medical sciences; Cell Line; Conjugation; Dextran; Dextrans - chemistry; Dextrans - pharmacology; Female; HIV Infections - drug therapy; HIV Infections - virology; HIV-1 - drug effects; HIV-1 - physiology; HIV-1 suppression; Human viral diseases; Humans; Immunodeficiencies; Immunodeficiencies. Immunoglobulinopathies; Immunopathology; Infectious diseases; Male; Medical sciences; Mice; Mice, Inbred BALB C; Pharmacology. Drug treatments; Polylysine - chemistry; Polylysine - pharmacology; Proteoglycans - chemistry; Proteoglycans - pharmacology; Pseudoproteoglycan; Unsulfated glycan; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Virus Internalization - drug effects; Virus Replication - drug effects; α-Polyl-lysine; Dextran; HIV-1 suppression; α-Polyl-lysine; Conjugation; Unsulfated glycan; Pseudoproteoglycan; Performance evaluation; Antiretroviral agent; HIV-1 virus; Suppression; Pharmacotherapy; Blood substitute; Antiviral; Drug; Immunopathology; Retroviridae; AIDS; Immune deficiency; Lentivirus; Glycan; Infection; Virus; Treatment; Lysine; Aminoacid; Viral disease; α-Poly L-lysine; Human immunodeficiency virus; Technique
• ISSN: 0166-3542; 1872-9096
• DOI: 10.1016/j.antiviral.2012.02.011

► Conjugation of dextran chains to a polyl-lysine produced a high anti-HIV-1 activity. ► The PLL–Dex suppressed both the macrophage-tropic R5 and T-cell line tropic X4 virus. ► The cytotoxicity of PLL was remarkably decreased by conjugation with Dex. ► PLL–Dex was effective against a clinically isolated R5 virus in primary PBMC. ► Acting both on cells and virus, PLL–Dex inhibits cell binding and entry of the virus. A conjugate of polyl-lysine (PLL) with unsulfated dextran produced by reductive amination was found to have remarkable anti-HIV-1 activity against both the macrophage-tropic R5 virus Ba-L and T-cell line tropic X4 virus IIIB strains, although neither PLL nor dextran has such activity. The conjugate is a pseudoproteoglycan (pseudoPG) that simulates the structure of a proteoglycan. Conjugation with dextran was found to produce an antiviral effect in three kinds of assay systems including a human CD4+ T-cell line, and the pseudoPG synthesized using 10kDa PLL and 10kDa dextran showed EC50 4–40 times lower than that of sulfated dextran or heparin against Ba-L and EC50 equal to that against IIIB, indicating that PLL–dextran (PLL–Dex) was more effective against R5 virus than sulfated polysaccharides. PLL–Dex significantly suppressed a clinically isolated R5 virus from primary peripheral blood mononuclear cells. PLL–Dex interacted with the virus during adsorption to the cell and also decreased virus entry into the cell, suggesting PLL–Dex has multiple preventive mechanisms against HIV-1.