Biology Reference
In-Depth Information
RNA viruses termed “human rhinoviruses” (HRVs). Much knowl-
edge stems from earlier studies of the related enteroviruses, in partic-
ular the polio virus and coxsackievirus, which are rather closely related
to HRVs; with due care, insight gained from work on enteroviruses
can often, but not always, be extrapolated to the rhinovirus field.
Physicochemically, rhinoviruses are distinguished from enteroviruses
based on their acid lability, a feature originally used for their classifi-
cation; enteroviruses, in contrast, remain infective at pH below 3;
thus, they can pass unharmed through the digestive tract. They infect
the intestinal epithelia and sometimes spread throughout the body,
causing viremia. Conversely, rhinoviruses are comparably harmless,
usually remaining confined to the upper respiratory tract and only
occasionally spreading to the lungs.
During the HRV infection cycle, the following sequence of events
can be differentiated: (1) virus binding to its receptors at the plasma
membrane; (2) entry into the cell by receptor-mediated endocytosis;
(3) conformational change of the viral capsid; (4) release of the viral
RNA (“uncoating”); (5) RNA penetration into the cytoplasm; (6) syn-
thesis of viral proteins; (7) RNA replication; and (8) assembly and
release of new, infectious virions.
HRVs are composed of a protein shell assembled from 60 copies
each of the four capsid proteins VP1, 2, 3, and 4. VP4 is internal
and in close proximity to the RNA; however, due to the dynamic
nature of the capsid, large parts of VP4 and the capsid-internal
N-terminus of VP1 become temporally exposed to the solvent, a
feature termed “breathing.”
2-6
The viral shell is about 30 nm in
diameter with the five-fold axes of icosahedral symmetry being sur-
rounded by a cleft, termed the canyon. It encloses a single-stranded
RNA genome of roughly 7100 bases. Upon arrival in the cytosol,
the RNA becomes translated into a polyprotein that is autocatalyti-
cally and co-translationally cleaved by the viral proteinases 2A
pro
,
3C
pro
and 3CD
pro
into VP1, VP0, VP3 and the non-structural pro-
teins. Maturation cleavage of VP0 into VP2 and VP4 occurs by an
unknown protease upon virus assembly. Not counting the precursor
proteins — such as 3CD, the precursor of the protease 3C
pro
and the
RNA-dependent RNA polymerase 3D
pol
— 11 mature polypeptides
are eventually generated from the polyprotein.
