The Arenaviridae are a
family of viruses whose members are generally associated with
rodent-transmitted disease in humans.
Arenaviruses are round, oval
, or pleomorphic with a range in size between 100 to 130 nm.
They are enveloped
particles, and the envelop contains club-shaped projections at its
surface.
Electron-dense granules are
found in variable numbers in the interior of the virions.
The granules are 20 to 25 nm
in diameter and represrnt host ribosomes.
The sandlike granules gave
the name to this group of viruses (arena, Latin for 'sand').
The genome of arenaviruses
consists of four pieces of single-stranded RNA and several small
pieces of RNA, some of which may be of host origin.
Rodents are the natural host
of arenaviruses, and humans are accidently infected when they come
into contact with infected urine.
Person-to-person spread is
unusual except for
lassa virus
.
The
arenaviruses are divided into two groups: the New World or Tacaribe
complex and the Old World or LCM/Lassa complex.
The relevant members of the
Arenaviridae family are
lymphocytic
choriomeningitis virus
, lassa virus
,
Junin virus (Argentine
hemorrhagic fever) ,
Machupo virus (Bolivian
hemorrhagic fever), Guanarito virus (Venezuelan hemorrhagic fever),
Sabia (Brazilian hemorrhagic fever).
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Arenaviruses. Curr Top Microbiol
Immunol. 2007;315:253-88.
The Arenaviridae family
contains 22 recognized virus species, each of them strongly
associated with a rodent species (except Tacaribe virus which is
associated with a species of bat), suggesting an ancient
co-evolutionary process. Although the concept of co-evolution
between rodents and arenaviruses is now largely accepted, little
has been uncovered in terms of dating the phenomenon and the
mechanisms of evolution, including speciation and pathogenicity.
These questions are targeted in the present chapter. Old World
arenaviruses are associated with the Eurasian rodents in the
family Muridae. New World arenaviruses are associated with
American rodents in the subfamily Sigmodontinae. The correlation
between the rodent host phylogeny and the viruses suggests a
long association and a co-evolutionary process. Furthermore,
three distinct New World arenaviruses share a common ancestor,
demonstrating a unique recombination event that probably
occurred in that ancestor. This shows that recombination among
arenaviruses of different lineages might occur in nature.
Recombination and co-evolutionary adaptation appear as the main
mechanisms of arenavirus evolution, generating a high degree of
diversity. The diversity among rodent host reservoir and virus
species and the potential to exchange genomic material provide a
basis for the emergence of new viruses and the risk of these
becoming pathogenic
Different mechanisms of cell entry by human pathogenic Old World
and New World arenaviruses.J
Virol. 2008 May 28.
The Old
World arenavirus Lassa virus (LASV) is the causative agent of a
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. The rescued rLCMV-LASVGP grew to titers comparable to 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. |
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