Abstract
Arenaviruses are a family of enveloped negative-stranded RNA viruses that can cause severe human disease ranging from encephalitis symptoms to fulminant hemorrhagic fever. The bi‑segmented RNA genome encodes four polypeptides: the nucleoprotein NP, the surface glycoprotein GP, the polymerase L, and the RING finger protein Z. Although it is the smallest arenavirus protein with a length of 90 to 99 amino acids and a molecular weight of approx. 11 kDa, the Z protein has multiple functions in the viral life cycle including (i) regulation of viral RNA synthesis, (ii) orchestration of viral assembly and budding, (iii) interaction with host cell proteins, and (iv) interferon antagonism. In this review, we summarize our current understanding of the structural and functional role of the Z protein in the arenavirus replication cycle.
Highlights
The Arenaviridae family consists of one unique genus (Arenavirus) that currently comprises 24 recognized virus species as defined by the International Committee on Taxonomy of Viruses.According to their antigenic properties, their serological relationships and their geographical distribution, arenaviruses have been classified into two groups: the New World (NW) and the OldWorld (OW) group (Fig. 1)
The OW group includes the globally distributed prototypic arenavirus, lymphocytic choriomeningitis virus (LCMV), as well as the highly human pathogenic Lassa virus (LASV), which is the causative agent of the acute viral hemorrhagic Lassa fever found in West Africa; and Lujo virus (LUJV) that has been associated with severe hemorrhagic fever disease in five patients in southern Africa [1,2,3]
In spite of the progress made in understanding the structural details of arenavirus glycoproteins, the intracellular trafficking pathway and the maturation of GP, the mechanism by which the tripartite mature GP complex is incorporated into the lipid bilayer of the nascent virions during virus assembly is still only partially understood
Summary
The Arenaviridae family consists of one unique genus (Arenavirus) that currently comprises 24 recognized virus species as defined by the International Committee on Taxonomy of Viruses According to their antigenic properties, their serological relationships and their geographical distribution, arenaviruses have been classified into two groups: the New World (NW) and the Old. World (OW) group (Fig. 1). Arenaviruses are lipid-enveloped viruses containing a bi-segmented negative-strand RNA genome. It is assumed that the lipid bilayer of the viral envelope derives from the host cell membrane where arenavirus budding occurs. The viral envelope, a lipid bilayer derived from the host cell plasma membrane, contains multiple copies of glycoprotein spikes on the surface that are required for receptor binding and virus entry. Recent studies demonstrated that LASV and LCMV cell entry occurs through late endosomes/multivesicular bodies (MVBs) This novel arenavirus entry pathway is thought to be linked to the cellular trafficking and degradation route of αdystroglycan [64].
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