Alphavirus
Alphavirus is a genus of RNA
viruses, the sole genus in the Togaviridae family. Alphaviruses belong to group
IV of the Baltimore classification of viruses, with a positive-sense,
single-stranded RNA genome. There are 32 alphaviruses, which infect various
vertebrates such as humans, rodents, fish, birds, and larger mammals such as
horses, as well as invertebrates. Alphaviruses that could infect both
vertebrates and arthropods are referred dual-host alphaviruses, while
insect-specific alphaviruses such as Eilat virus and Yada yada virus are
restricted to their competent arthropod vector. Transmission between species
and individuals occurs mainly via mosquitoes, making the alphaviruses a member
of the collection of arboviruses – or arthropod-borne viruses. Alphavirus
particles are enveloped, have a 70 nm diameter, tend to be spherical (although
slightly pleomorphic), and have a 40 nm isometric nucleocapsid.
The alphaviruses are small,
spherical, enveloped viruses with a genome of a single strand of positive-sense
RNA. The total genome length ranges between 11,000 and 12,000 nucleotides, and
has a 5’ cap and a 3’ poly-A tail. The four non-structural protein genes are
encoded in the 5′ two-thirds of the genome, while the three structural proteins
are translated from a subgenomic mRNA colinear with the 3′ one-third of the
genome.
There are two open reading
frames (ORFs) in the genome, nonstructural and structural. The first is
non-structural and encodes proteins (nsP1–nsP4) necessary for transcription and
replication of viral RNA. The second encodes three structural proteins: the core
nucleocapsid protein C, and the envelope proteins P62 and E1, which associate
as a heterodimer. The viral membrane-anchored surface glycoproteins are
responsible for receptor recognition and entry into target cells through
membrane fusion.
The proteolytic maturation
of P62 into E2 and E3 causes a change in the viral surface. Together the E1,
E2, and sometimes E3, glycoprotein "spikes" form an E1/E2 dimer or an
E1/E2/E3 trimer, where E2 extends from the centre to the vertices, E1 fills the
space between the vertices, and E3, if present, is at the distal end of the
spike. exposure of the virus to the acidity of the
endosome, E1 dissociates from E2 to form an E1 homotrimer, which is necessary
for the fusion step to drive the cellular and viral membranes together. The
alphaviral glycoprotein E1 is a class II viral fusion protein, which is
structurally different from the class I fusion proteins found in influenza
virus and HIV. The structure of the Semliki Forest virus revealed a structure
that is similar to that of flaviviral glycoprotein E, with three structural
domains in the same primary sequence arrangement. The E2 glycoprotein functions
to interact with the nucleocapsid through its cytoplasmic domain, while its
ectodomain is responsible for binding a cellular receptor. Most alphaviruses
lose the peripheral protein E3, but in Semliki viruses it remains associated
with the viral surface.
Nonstructural proteins. Four nonstructural proteins (nsP1–4) which
are produced as a single polyprotein constitute the virus' replication
machinery. The processing of the polyprotein occurs in a highly regulated
manner, with cleavage at the P2/3 junction influencing RNA template use during
genome replication. This site is located at the base of a narrow cleft and is
not readily accessible. Once cleaved nsP3 creates a ring structure that
encircles nsP2. These two proteins have an extensive interface. Mutations in nsP2 that produce noncytopathic
viruses or a temperature sensitive phenotypes cluster at the P2/P3 interface
region. P3 mutations opposite the location of the nsP2 noncytopathic mutations
prevent efficient cleavage of P2/3. This in turn affects RNA infectivity
altering viral RNA production levels.
Virology. The virus has a 60–70 nanometer diameter. It
is enveloped, spherical and has a positive-strand RNA genome of ~12 kilobases.
The genome encodes two polyproteins. The first polyprotein consists of four
non-structural units: in order from the N terminal to the C terminal - nsP1,
nsP2, nsP3, and nsP4. The second is a structural polyprotein composed of five
expression units: from the N terminal to the C terminal - Capsid, E3, E2, 6K
and E1. A sub genomic positive strand RNA - the 26S RNA - is replicated from a
negative-stranded RNA intermediate. This serves as template for the synthesis
of viral structural proteins. Most alphaviruses have conserved domains involved
in regulation of viral RNA synthesis.
The nucleocapsid, 40 nanometers in diameter, contains 240 copies of the
capsid protein and has a T = 4 icosahedral symmetry. The E1 and E2 viral
glycoproteins are embedded in the lipid bilayer. Single E1 and E2 molecules
associate to form heterodimers. The E1–E2 heterodimers form one-to-one contacts
between the E2 protein and the nucleocapsid monomers. The E1 and E2 proteins
mediate contact between the virus and the host cell.
Several receptors have been identified. These
include prohibition, phosphatidylserine, glycosaminoglycans and ATP synthase β
subunit. Replication occurs within the
cytoplasm, specifically in areas termed "spherules" separated by
plasma membrane invaginations from the rest. Each complex occupies one such
area of about 50-nm in inner diameter.
Virions mature by budding through the plasma membrane, where
virus-encoded surface glycoproteins E2 and E1 are assimilated. These two
glycoproteins are the targets of numerous serologic reactions and tests
including neutralization and hemagglutination inhibition. The alphaviruses show
various degrees of antigenic cross-reactivity in these reactions and this forms
the basis for the seven antigenic complexes, 32 species and many subtypes and
varieties. The E2 protein is the site of most neutralizing epitopes, while the
E1 protein contains more conserved, cross-reactive epitopes.
Evolution. A study of this taxon suggests that this
group of viruses had a marine origin—specifically the Southern Ocean—and that
they have subsequently spread to both the Old and New World. There are three subgroups in this genus: the
Semliki Forest virus subgroup (Semliki Forest, O'nyong-nyong and Ross River
viruses); the eastern equine encephalitis virus subgroup (eastern equine
encephalitis and Venezuelan equine encephalitis viruses) and the Sindbis virus
subgroup. Sindbis virus, geographically restricted to
the Old World, is more closely related to the eastern equine encephalitis
subgroup, which are New World viruses, than it is to the Semliki Forest virus
subgroup which is also found in the Old World.
Taxonomy
The following species are
assigned to the genus:
Aura virus
Barmah Forest virus
Bebaru virus
Caaingua virus
Cabassou virus
Chikungunya virus
Eastern equine encephalitis
virus
Eilat virus
Everglades virus
Fort Morgan virus
Getah virus
Highlands J virus
Madariaga virus
Mayaro virus
Middelburg virus
Mosso das Pedras virus
Mucambo virus
Ndumu virus
O'nyong'nyong virus
Pixuna virus
Rio Negro virus
Ross River virus
Salmon pancreas disease virus
Semliki Forest virus
Sindbis virus
Southern elephant seal virus
Tonate virus
Trocara virus
Una virus
Venezuelan equine
encephalitis virus
Western equine encephalitis
virus
Whataroa virus
Jan Ricks Jennings, MHA,
LFACHE
Senior Consultant
Senior Management
Resources, LLC
JanJenningsBlog.Blogspot.com
412.913.0636 Cell
724.733.0509 Office
September 19, 2022
No comments:
Post a Comment