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capsid gene expression has been reported. 20 This region has also been
identified as a hotspot for RNA recombination. 21
Proteolytic Processing
As illustrated in Fig. 2, the polyprotein precursor would be cleaved
intracellularly by cellular proteases and extracellularly by trypsin to
produce three mature structural proteins of 32-34 kDa (VP34),
29-31 kDa (VP29), and 24-26 kDa (VP26), with molecular weights
and trypsin cleavage sites varying between different serotypes. 8,15,22-24
In studies based on HAstV-2, it was found that the 87 kDa polypro-
tein could be assembled into particles and then cleaved into proteins
of 32, 29 and 26 kDa. 24,25 Bass and Qiu suggested that assembly of
HAstV-1 particles requires an intracellular cleavage of the first 70
N-terminal amino acids of the 87 kDa precursor protein. 22 The result-
ant 79 kDa protein would assemble into the viral capsid within
infected cells. In the absence of trypsin, these particles are virtually
noninfectious, but they can become infectious when trypsin cleaves
the 79 kDa protein into the final structural proteins VP34, VP29 and
VP26. This intracellular cleavage at the N-terminus was not observed
in other studies with HAstV-1 26 and HAstV-8 8 infected cells, but it
has recently been demonstrated for HAstV-1 that the 70 amino acids
at the N-terminus of the polyprotein are not essential to assemble into
virus-like particles. 27
An extensive study using HAstV-8 demonstrated that the 90 kDa
polyprotein (VP90) is first cleaved intracellularly at its C-terminus,
giving rise to a 70 kDa protein (VP70) that is mainly found into puri-
fied particles. 8 The VP70-containing virus is minimally infectious and
requires trypsin to enhance its infectivity. Following trypsin activation,
VP70 is processed into the three predominant smaller mature prod-
ucts. In a later study, the same authors observed that indeed the
capsid precursor VP90 is able to assemble into virions, as it had
been shown to do in other studies for HAstV-1 26 and HAstV-2. 24,25
However, these resulting particles were relatively unstable and would
disassemble during cesium chloride purification, indicating that the
cleavage that yields VP70 structurally stabilizes the viral particles. 23
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