Biology Reference
In-Depth Information
that the C-terminal protein of nsP1a colocalizes with the endoplasmic
reticulum and viral RNA in HAstV-4 CaCo-2 infected cells, suggest-
ing the involvement of this protein in the RNA replication process in
endoplasmic reticulum-derived intracellular membranes.
47
Computer analysis of nsP1a has recently revealed the presence of
two coiled-coil regions (CC) common to all known human astro-
viruses, which are hypothesized to be involved in the formation of pro-
tein oligomers.
20
The absence of a methyltransferase-encoding region
and the similarity of the HAstV RNA-dependent RNA polymerase
motif with primarily polymerases of VPg-containing viruses raise the
possibility that the HAstV genome, as well as the subgenomic RNA,
may be linked to a VPg protein in its 5'-end. A convincing VPg domain
has not been identified, but it may be located upstream from the pro-
tease motif, where it has been postulated that Ser
420
could link the
VPg to viral RNA.
11
However, based on sequence comparison between
human and animal astroviruses with some members of the
Caliciviri-
dae
,
Picornaviridae
and
Potyviridae
families, other authors have also
suggested that amino acid Tyr
693
at the conserved TEEEY-like motif
could also display a VPg function.
17,20
Indeed, one of the conserved
amino acid motifs characteristic of VPg of caliciviruses [KGK(N/T)K]
52
can also be identified upstream from this Tyr
693
residue at a similar
distance as it is found in the calicivirus genome.
Finally, it has recently been reported that products derived from
nsP1a lead to apoptosis of the host cell, resulting in efficient virus
replication and particle release.
23,28
The analysis of the secondary struc-
ture of the whole astrovirus protein sequence revealed the presence of
an optimal six
-helix structure of 95 amino acids close to the C-ter-
minus of nsP1a, which displays homology to the death domain super-
family.
28
The presence of a putative death domain in nsP1a suggests a
direct link between this polyprotein and the apoptotic pathway.
α
Proteolytic Processing
The proteolytic processing of the HAstV nsP1a polyprotein (920-935
amino acids, depending on serotype) has been only partially charac-
terized, and some of the reported data are still conflicting.
40,46,48,53,54
