Filovirus Tropism: Cellular Molecules for Viral Entry

Takada, Ayato

Ebola virus and Marburg virus are filamentous, enveloped, non-segmented, single-stranded, negative-sense RNA viruses (Figure 2) . The viral genome 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). EBOV also expresses at least one secreted nonstructural glycoprotein (sGP). Figure 3 summarizes filovirus replication in cells. At the first step of replication, viral attachment through interaction between GP and some cellular molecules is followed by endocytosis, including macropinocytosis (Nanbo et al., 2010; Saeed et al., 2010) . Subsequent fusion of the viral envelope with the host cell endosomal membrane releases the viral proteins (i.e., NP, VP35, VP30, and L) and RNA genome into the cytoplasm, the site of replication. Transcription of the negative-sense viral RNA by the viral polymerase complex (VP35 and L) yields mRNAs that are translated at cellular ribosomes. During replication, full-length positive-sense copies of the viral genome are synthesized. They subsequently serve as templates for replication of negative-sense viral RNA synthesis. At the plasma membrane, NP-encapsidated full-length viral RNAs and the other viral structural proteins are assembled with VP40 and GP and incorporated into enveloped virus particles that bud from the cellsurface (Noda et al., 2006; Bharat et al., 2011) . Though filoviruses show broad tissue tropism, hepatocytes, endothelial cells, dendritic cells, monocytes, and macrophages are thought to be their preferred target cells, and infection of these cells is important for hemorrhagic manifestation and immune disorders (Geisbert and Hensley, 2004) .