Filovirus

Filovirus

Filoviruses belong to a virus family called Filoviridae and can cause severe hemorrhagic fever in humans and nonhuman primates. So far, only two members of this virus family have been identified: Marburgvirus and Ebolavirus.

The filoviruses are so named because of their long, filamentous morphology. Although the particles are pleomorphic and can vary substantially in length (~650 - ~1,400 nm), the diameter maintains a constant size of 80 nm. The genome of all viruses within the Mononegavirales order is a linear, single-stranded, negative sense RNA molecule. Although rare, filovirus infection can be devastating, with case fatality rates of over 90% reported in some outbreaks. Although there are a few promising vaccine and therapeutic candidates under development, there are currently no prophylaxes or treatments approved for filovirus infection in the United States. Therefore, these viruses have been classified as Category A Biodefense pathogens by the National Institute for Allergy and Infectious Disease (NIAID), and must be dealt with under Biosafety Level 4 (BSL-4) conditions.

Structure of Filovirus Particles

They display a uniform diameter of approximately 80 nm, but vary greatly in length. Negatively contrasted particles, regardless of serotype or host cell, contain an electron-dense central axis (19-25 nm in diameter) surrounded by an outer helical layer (45-50 nm in diameter) with cross-striations at 5 nm intervals. This central core is formed by the RNP complex, which is surrounded by a lipid envelope derived from the host cell plasma membrane. Spikes of approximately 7 nm in diameter and spaced at about 5-10 nm intervals are seen as globular structures on the surface of virions. Virus particles are made of seven structural proteins with presumed identical functions for the different viruses. Four proteins make up the RNP complex [nucleoprotein (NP), virion protein (VP) 35, VP30 and RNA-dependent-RNA polymerase (L)] together with the viral RNA, while the remaining three proteins are membrane-associated [glycoprotein (GP), VP40, VP24].

Species of Filovirus

Marburgvirus and Ebolavirus are two members of the Filoviridae family of viruses (the filoviruses), of the order Mononegavirales. The filoviruses are highly pathogenic, causing severe hemorrhagic fever in humans and non-human primates as well as other mammals. There are two known species of Marburgvirus: Marburg Virus (MARV) and Ravn virus (RAVV ), Clinical infection by MARV and RAVV are indistinguishable, and the two viral strains have been observed to co-circulate in some outbreaks of Marburg hemorrhagic fever. Therefore, for simplicity, “MARV” is used to describe both MARV and RAVV throughout this thesis.

Five species of Ebolavirus have been identified: Zaire (EBOV), Sudan (SUDV), Bundibugyo (BDBV), Tai Forest (TAFV), and Reston (RESTV), Although the viral strains share many common features (genomic organization, general mechanism of viral entry and propagation, etc), the pathogenicity of these viruses in humans varies greatly. EBOV and SUDV were the first Ebolavirus strains to be identified, making anappearance nearly a decade after the emergence of MARV, with simultaneous outbreaks occurring in 1976 in Zaire (currently the Democratic Republic of Congo) (EBOV) and Sudan (SUDV). EBOV is the deadliest of the filoviruses, with case fatality rates ranging from 46% to greater than 90%. SUDV is also highly pathogenic, with case fatality rates of 41-71%. Together, EBOV and SUDV have been responsible for the majority of filovirus outbreaks and have caused -80% of all filovirus-related deaths. BDBV has been implicated in two large outbreaks, with an average case fatality rate of ~40%. TAFV was identified in a single non-fatal case in 1994. RESTV was discovered in 1989 during an outbreak of hemorrhagic fever deaths in non-humanprimates in an animal holding facility in Reston, Virginia. Although RESTV causes high fatality rates in non-human primates, it appears to be non-pathologic to humans; RESTV has caused no symptoms even in individuals with serologic evidence for infection.

References:

Theriault, Steven S. "The role of reverse genetics systems in the study of filovirus pathogenicity." (2006).

Koellhoffer, Jayne F.Intermediates of Filovirus Membrane Fusion Explored Through Antibody Engineering and Protein Design. Yeshiva University, 2013.

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