Role of Gangliosides in Reception of Influenza Virus

Abstract

The ganglioside composition of Ehrlich ascites carcinoma (EAC) cells and the role of the individual gangliosides in binding and penetration into the cell of influenza virus were determined. EAC gangliosides identical with or close t o G M~. GMZ, G M~, G T~~ and G T I~ were characterized by thin-layer chromarography, compositional analyses, methylation analysis and mass-spectrometry. The ganglioside uptake capacity of native and neuraminidase-treated EAC cells was studied with tritium-labeled gangliosides of definite structure and the binding of influenza virus to cells was determinated by using ["Hluridine-labeled virus and by heinagglutination studies. Treatment of the cells with Vihrio c l t o l~~r n~~ neuraminidase largely decreased binding of the virus. Exogenous gangliosides with a terminal galactose unit or a penultimate galactose masked by neuraminic acid were able to restore the virus-binding capacity of ncuraminidase-treated cells, however, the main ganglioside of EAC cells, Ghfz, which carbohydrate chain is terminated by N-acetylgalactosamine, was completely ineffective. The common carbohydrate sequence of the gangliosides showing binding activityis proposed to be the main recognition structure of the influenza virus receptor on the surface of EAC cells. Penetration of labeled influenza virus into the nuclei of EAC cells was evaluated by measuring the radioactivity of the nuclei of neuraminidase-treated ganglioside-loaded cells after exposition to the labeled virus. Of all gangliosides tested only trisialogangliosidcs of the G~l b type were able to induce increased entry of the virus into the cells and accumulation of its radioactive component into the nuclei. It is suggested that G T I~ gangliosides react specifically with the virus protein responsible for membrane fusion (apparently the hemagglutinin HA2 subunit) and thus are involved in virus penetration and delivery of the virus genome to the nuclei.When interacting with cells ortho-and paramyxoviruses first adsorb to specific host receptors and then penetrate thc cell. While nothing is known about the nature of the cell surface components involved in the penetration process, some information about the receptors responsible for adsorbtion of the viruses is available. The receptors contain neuraminic acid and their receptor activity is destroyed by neuraminidase [2]. It is therefore thought that glycoproteins [3 -51 or sialoglycolipids (gangliosides) [6 -81 serve as receptors.Comparing the virus-binding activity of glycoproteins isolated from HeLa cells and brain gangliosides, Wu et al.", I showed that adsorbtion of Sendai virus required much less glycoprotein than glycolipid and concluded that the former are responsible for virus attachment. However recently it hdS been demonstrated that di-, tri-and tetrasialogangliosides can function as receptors for Sendai virus in cultured bovine kidney cells [lo, 1 11. Thus, the existing evidence of participitation of gangliosides in virus-cell association is contradictive. Moreover, the data obtained so far d...

Sialidase Fusion Protein as a Novel Broad-Spectrum Inhibitor of Influenza Virus Infection

“…In several experiments performed much later, MDCK (Madin-Darby canine kidney) or EAC (Ehrlich ascites carcinoma) cells were briefly treated with Vibrio cholerae sialidase and then infected with influenza virus. Influenza virus infections were decreased by 90 to 100% as a result of the sialidase treatment (6,13,52). Micromonospora viridifaciens sialidase was also used to destroy cellular influenza virus receptors in cell culture assays (2).…”

Gangliosides Have a Functional Role during Rotavirus Cell Entry

“…Besides these important biological functions they are also used as receptors for many viruses, including different members of the Polyomaviridae family (simian virus 40, murine polyomavirus, BK virus, JC virus, Merkel cell polyomavirus) (14,15), paramyxoviruses (Newcastle disease virus and Sendai virus) (16), bovine adeno-associated virus (17), influenza virus (18), murine norovirus (19), and rotavirus (10,20).…”

Gangliosides Act as Co-receptors for Salmonella enteritidis FliC and Promote FliC Induction of Human β-Defensin-2 Expression in Caco-2 Cells

“…Gangliosides, sialic acid-containing glycosphingolipids, are ubiquitous components of eukaryotic cell membranes that have been identified as receptors for bacterial toxins and viruses (27)(28)(29)(30). Although TLR5 was determined to be a FliC receptor, gangliosides such as GM1, GD1a, and asialo-GM1 also bound Pseudomonas aeruginosa flagellin (31).…”