Different mechanisms of cell entry by human-pathogenic Old World and New World arenaviruses.

Details

Serval ID
serval:BIB_C0244F411684
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Different mechanisms of cell entry by human-pathogenic Old World and New World arenaviruses.
Journal
Journal of Virology
Author(s)
Rojek J.M., Sanchez A.B., Nguyen N.T., de la Torre J.C., Kunz S.
ISSN
1098-5514 (Electronic)
ISSN-L
0022-538X
Publication state
Published
Issued date
2008
Volume
82
Number
15
Pages
7677-7687
Language
english
Abstract
The Old World arenavirus Lassa virus (LASV) is the causative agent of severe viral hemorrhagic fever (VHF) in humans and is the most prevalent human pathogen among arenaviruses. The present study investigated the largely unknown mechanisms of cell entry of LASV, a process know to be mediated solely by the virus envelope glycoprotein (GP). To circumvent biosafety restrictions associated with the use of live LASV, we used reverse genetics to generate a recombinant variant of the prototypic arenavirus lymphocytic choriomeningitis virus (LCMV) expressing the LASV GP (rLCMV-LASVGP). The rescued rLCMV-LASVGP grew to titers comparable to that of LCMV and showed the receptor binding characteristics of LASV. We used rLCMV-LASVGP to characterize the cellular mechanisms of LASV entry in the context of a productive arenavirus infection. The kinetics of pH-dependent membrane fusion of rLCMV-LASVGP resembled those of the human-pathogenic New World arenavirus Junin virus (JUNV) and other enveloped viruses that use clathrin-mediated endocytosis for entry. However, rLCMV-LASVGP entered cells predominantly via a clathrin-, caveolin-, and dynamin-independent endocytotic pathway similar to the one recently described for LCMV. Productive infection of rLCMV-LASVGP was only mildly affected by a dominant negative mutant of Rab5 and was independent of Rab7, suggesting an unusual mechanism of delivery to endosomes. In addition, rLCMV-LASVGP infection was independent of actin but required intact microtubules. Our data indicate that LASV enters cells via a pathway distinct from the one used by human-pathogenic New World arenaviruses.
Keywords
Actins/genetics, Animals, Arenaviruses, New World/physiology, Arenaviruses, Old World/physiology, Cell Line, Cercopithecus aethiops, Cricetinae, Endocytosis, Endosomes/virology, Humans, Hydrogen-Ion Concentration, Lassa virus/genetics, Lymphocytic choriomeningitis virus/genetics, Microtubules/virology, Time Factors, Virus Internalization, rab GTP-Binding Proteins/genetics, rab5 GTP-Binding Proteins/genetics
Pubmed
Web of science
Open Access
Yes
Create date
17/04/2013 12:56
Last modification date
20/08/2019 16:34
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