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part influenced the cross-reactivity among the GII/3 VLPs (i.e. with-
out the helix structure, GII/3 1152 VLPs cross-react weakly against
the other four GII/3 antisera). This suggestion may also explain NoV
virulence in which some strains appear to infect a certain population
over an extended period of time. 40,41 In a recent report, single amino
acid changes were suggested to represent a possible way for the virus
to evade the host immunity. 40 In addition, one report suggested a
change in the VP1 secondary structure (i.e. a disappearance of a helix
structure) was responsible for a chronic NoV infection in an immuno-
compromised patient for over two years. 42 Furthermore, the helix
structure reported by Nilsson et al . was located near the helix structure
described in Fig. 5, signifying an important antigenic site.
Proteolytic and Replication
Proteolytic and replication studies on human caliciviruses have been
enigmatic due to their inability to grow in conventional cell cultures.
Development of a self-replicating complete VLP (i.e. containing RNA)
would greatly enhance the understanding of infectivity, antigenicity,
and binding factors. Nevertheless, a number of important proteolytic
and replication studies have been conducted. Proteolytic processing of
the ORF1 polyprotein is a common feature of the caliciviruses. 43 The
cleavage sites have been mapped in detail in RHDV, 44-48 FCV, 49-51 and
NoV, 52-59 and more recently the cleavage map of a SaV was deter-
mined. 60 Site-directed mutagenesis demonstrated that the P1 amino
acid (i.e. the amino acid immediately upstream of the scissile bond)
plays a critical role in the proteolytic processing. The importance of
phenylalanine at the P4 position to achieve efficient cleavage between
N-terminal protein and NTPase of NoV was noted by Hardy et al . 54
Similarly, a phenylalanine residue was found at the P4 position in
three of five cleavage sites in the ORF1 and at one cleavage site in the
ORF2 of FCV. Although the details of the calicivirus genome repli-
cation, transcription, and translation remain unclear, the translation
might require a cap or a cap-like structure, or VPg attached to the 5ยด
end of the genome and subgenome as reported in FCV. 61,62 Recently,
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