Marburgviruses: An Update

Caterina M. Miraglia, DC, MLS(ASCP)

Disclosures

Lab Med. 2019;50(1):16-28. 

In This Article

Viral Characteristics

Marburgviruses belong to the family Filoviridae, along with ebolaviruses. Members of this family cause fulminant hemorrhagic fever in humans and nonhuman primates (NHPs). These viruses are pleomorphic, appearing as filaments, circles, or a "number 6" formation.[3] On average, filamentous virons are 892 nm long and have a diameter of 91 nm[4] (Image 1).

Image 1.

Transmission electron micrograph demonstrating the morphology of Marburg virus virions. This image is in the public domain and therefore free of any copyright restrictions. The image is courtesy of the Centers for Disease Control and Prevention (CDC) Public Health Image Library, ID#1873, and is available at https://phil.cdc.gov/phil/details.asp, selected keywords: Marburg virus electron micrograph.

MARV was the first filovirus discovered; it was identified by electron microscopy in 1967. Ebolaviruses were discovered in 1976 during an outbreak of viral hemorrhagic fever (VHF) in Zaire (present-day Democratic Republic of Congo) and Sudan.[3,5] Table 1 provides a complete history of known Marburg virus disease (MVD) cases and outbreaks.[6–17]

The International Committee on Taxonomy of Viruses (ICTV) states that the family Filoviridae, in the order Mononegavirales, currently has 3 genera and 7 species. The 3 genera are Marburgvirus, Cuevavirus, and Ebolavirus. The genus Marburgvirus includes a single species, Marburg marburgvirus, which has 2 members: Marburg virus (MARV) and Ravn virus (RAVV). The genus Cuevavirus includes a single species, Lloviu cuevavirus, member Lloviu virus (LLOV); the genus Ebolavirus contains 5 species: Zaire ebolavirus (member: EBOV), Bundibugyo ebolavirus (member: Bundibugyo virus [BDBV]), Taï Forest ebolavirus (member: Taï Forest virus [TAFV]), Sudan ebolavirus(member: Sudan virus [SUDV]), and Reston ebolavirus (member: Reston virus [RESTV]).[18] Classification of filoviruses into genus and species is now performed using genomic sequence data and requires 55% to 58% and 23% to 36% sequence diversity thresholds, respectively.[19]

Filoviruses are lipid-enveloped viruses that have a negative-sense RNA genome that is approximately 19 kB long and codes for 7 proteins. Glycoprotein (GP) is a transmembrane surface protein that is responsible for binding to host cellular receptors and viral/host membrane fusion. Viral protein (VP)40 is a matrix protein involved in transferring nucleocapsids to the plasma membrane and budding of the virus from the host cell. VP24 is involved in nucleocapsid formation and assembly. Nucleoprotein (NP), VP35 (polymerase cofactor), VP30 (transcription activator), and L (RNA-dependent RNA polymerase) are proteins that make up the nucleocapsid.[20]

After the filovirus gains entry into the host, its GP binds to host cellular receptors. Next, the virus is taken into the cell by macropinocytosis and the virus is contained within a host cell membrane–derived endosome. When the endosome becomes acidified, the lysosomal proteases cathepsins B and L cleave the viral GP, enabling it to bind to the host receptor Niemann-Pick-1 (NPC1). This process allows for fusion of the viral and endosome membranes, and nucleocapsid is released into the cytoplasm, where transcription, translation, and replication occur. Viral components are assembled at the host cell membrane, and viral particles bud from the cell in a lipid envelope derived from the host cell membrane.[21]

Comments

3090D553-9492-4563-8681-AD288FA52ACE

processing....