Biology Reference
In-Depth Information
Capsid Protein Maturation and Apoptosis
The fact that HAstV infection induces apoptosis on CaCo-2 cells and
that apoptotic death of host cells seems necessary for efficient human
astrovirus replication and particle maturation has been demonstrated
by different authors.
23,28
Guix
et al
. observed that in the presence of a
caspase 8-specific inhibitor, there was a significant reduction in the
infectivity of the virus progeny, while the titer of physical virions in
cell supernatants estimated by ELISA and RT-PCR was not affected.
28
Méndez
et al
. demonstrated that VP90-VP70 processing is mediated
by caspases, and also observed that the release of infectious viruses
to the cell supernatant was reduced in the presence of a pancaspase
inhibitor and increased by the TNF-related apoptosis-inducing lig-
and (TRAIL).
23
However, inhibition of apoptosis also resulted in a
decrease in the total amount of viral protein detected in cell super-
natants, suggesting that processing of VP90 and/or the apoptotic cell
response may also affect viral release.
23
Differences between the condi-
tions of infections and the techniques used to measure the amount of
released viruses could partially explain these discrepancies. For several
viruses it has been observed that some of their proteins, both struc-
tural and nonstructural, undergo caspase-mediated proteolysis within
the host cell,
29-34
and in some cases such as human influenza virus or
Aleutian mink disease parvovirus, these cleavages are relevant for virus
replication and morphogenesis.
30,34
Structural Studies
Very little is known about the structural features of the HAstV
capsid, and most of our current knowledge comes from structural
predictions and comparison to other related viral families (for a review
see Krishna, 2005).
35
Based on the homology between different
astroviruses, the ORF2 sequence is divided into two regions. At the
N-terminus, region I spans amino acid residues 1 to 415 and is highly
conserved among all members of the
Astroviridae
family, while region
II at the C-terminus is extremely variable among different strains
