Filovirus Tropism: Cellular Molecules for Viral Entry

Abstract

In human and non-human primates, filoviruses (Ebola and Marburg viruses) cause severe hemorrhagic fever. Recently, other animals such as pigs and some species of fruit bats have also been shown to be susceptible to these viruses. While having a preference for some cell types such as hepatocytes, endothelial cells, dendritic cells, monocytes, and macrophages, filoviruses are known to be pantropic in infection of primates. The envelope glycoprotein (GP) is responsible for both receptor binding and fusion of the virus envelope with the host cell membrane. It has been demonstrated that filovirus GP interacts with multiple molecules for entry into host cells, whereas none of the cellular molecules so far identified as a receptor/co-receptor fully explains filovirus tissue tropism and host range. Available data suggest that the mucin-like region (MLR) on GP plays an important role in attachment to the preferred target cells, whose infection is likely involved in filovirus pathogenesis, whereas the MLR is not essential for the fundamental function of the GP in viral entry into cells in vitro. Further studies elucidating the mechanisms of cellular entry of filoviruses may shed light on the development of strategies for prophylaxis and treatment of Ebola and Marburg hemorrhagic fevers.

Enhancement of Ebola Virus Infection via Ficolin-1 Interaction with the Mucin Domain of GP Glycoprotein

“…Thus, the MBL and ficolin-1 receptor remains to be identified, and they may have different receptors, depending on the host cell type. It should be mentioned that this receptor might also serve as the unknown C1q receptor used to mediate antibody-dependent enhancement of viral infection (77) (Fig. 8).…”

“…Other membrane-anchored C-type lectin receptors, including the asialoglycoprotein receptor in hepatocytes, the dendritic cellspecific DC-SIGN, the liver/lymph node-specific lectins L-SIGN and LSECtin, and human macrophage lectin MGL (which are not present on the Vero E6 cells used in this study; reviewed in reference 77), have been shown to bind to the EBOV GP and to promote virus entry into various cell types. Binding of these lectins to EBOV GP was proposed to involve the mannose and/or GlcNAc residues of the N-linked carbohydrates present in the MLD or in the glycan cap.…”

Past, Present and Future about Ebola Virus Diseases: An Updated Review

“…[28][29][30][31][32][33][34][35][36][37][38] There is also a need to increase health workers' understanding on Ebola disease to improve healthcare like any other viral disease. [39] …”

Ebola Virus ? A Global Threat

“…31,32 The EBOV genome is about 19000 nucleotides long that encodes seven structural proteins, nucleoprotein (NP), polymerase cofactor (VP35), matrix protein (VP40), glycoprotein (GP), replication-transcription protein (VP30), minor matrix protein (VP24) and RNA-dependent RNA polymerase (L). 33,34 The structural proteins VP40 and VP24 represent viral matrix proteins connecting the nucleocapsid with the viral envelope.…”

“…Though Ebola shows broad tissue tropism, hepatocytes, endothelial cells, dendritic cells, monocytes, and macrophages are thought to be their preferred target cells. 31 Infection begins with the attachment of the virion to a receptor or lectin on the cell surface. Binding is followed by endocytosis, fusion of the viral envelope with the cellular endosomal membrane and release of the RNA genome and viral proteins into the cytoplasm.…”