Apolipoprotein A-I and its amphipathic helix peptide analogues inhibit human immunodeficiency virus-induced syncytium formation.

Abstract

The envelope (membrane) glycoprotein of HIV is essential for virus attachment and entry into host cells. Additionally, when expressed on the plasma membrane of infected cells, the envelope protein is responsible for mediating cell-cell fusion which leads to the formation of multinucleated giant cells, one of the major cytopathic effects of HIV infections. The envelope glycoproteins of HIV contain regions that can fold into amphipathic alpha-helixes, and these regions have been suggested to play a role in subunit associations and in virus-induced cell fusion and cytopathic effects of HIV. We therefore tested the possibility that amphipathic helix-containing peptides and proteins may interfere with the HIV amphipathic peptides and inhibit those steps of HIV infection involving membrane fusion. Apolipoprotein A-I, the major protein component of high density lipoprotein, and its amphipathic peptide analogue were found to inhibit cell fusion, both in HIV-1-infected T cells and in recombinant vaccinia-virus-infected CD4+ HeLa cells expressing HIV envelope protein on their surfaces. The amphipathic peptides inhibited the infectivity of HIV-1. The inhibitory effects were manifest when the virus, but not cells, was pretreated with the peptides. Also, a reduction in HIV-induced cell killing was observed when virus-infected cell cultures were maintained in presence of amphipathic peptides. These results have potential implications for HIV biology and therapy.

Influenza Infection Promotes Macrophage Traffic Into Arteries of Mice That Is Prevented by D-4F, an Apolipoprotein A-I Mimetic Peptide

“…These results demonstrate that D-4F may be acting through multiple pathways. Taken together with previous reports, 4,11,15,[22][23][24] our results suggest that apoA-I and apoA-I mimetic peptides such as D-4F are potent antiinflammatory agents that may have therapeutic potential.…”

“…Based on previous studies in vitro, 23,24 we measured viral titers in lungs from PBS-or D-4F-treated mice before and at 6 macrophages from male donors. At euthanasia, heart was perfused, aortic arch and innominate artery were removed by dissection, and contents of Sry DNA were determined as described in Methods.…”

A Study to Evaluate Lipid Profile in Treatment Naïve HIV Positive Patients

“…Zangerle et al reported a decrease in HDL in patients CD4 count \ 500, while no difference in others plasma lipids were seen. A high level of HDL may be protective against HIV, since apo A1, the main lipoprotein of HDL, inhibits syncytium formation [35]. In our study, LDL-C shows no correlation with CD4 counts or clinical staging.…”

Thematic review series: The Pathogenesis of Atherosclerosis. Effects of infection and inflammation on lipid and lipoprotein metabolism mechanisms and consequences to the host

“…These include New Castle disease virus, Rabies virus, Vesicular stomatitis virus, Japanese encephalitis virus, Rubella virus, Epstein-Barr virus, Herpes simplex virus, HIV, Simian immunodeficiency virus, Xenotropic virus, Sindbis virus, Vaccinia virus, Coxsackie virus, Poliovirus, and Mengo virus (345)(346)(347)(348)(349)(350)(351)(352)(353)(354)(355)(356). VLDL and LDL are particularly active against certain viruses, such as togaviruses (Japanese encephalitis virus and Rubella virus) and rhabdoviruses (Rabies virus and Vesicular stomatitis virus), whereas HDL displays a broader antiviral activity (347,349,356).…”