Biology Reference
In-Depth Information
receptor-mediated release or endocytosis of a partially tegumented
capsid, respectively. The cytoskeletal network, including the dynein and
dynactin components, is used to transport capsids to the nuclear pores.
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The DNA is injected into the nucleus, while the empty capsids remain
outside.
In the nucleus, the DNA circularizes and one of two pathways, i.e.
latent or lytic replications, is initiated. The viral genome can be main-
tained as a circular episome and undergo latent replication without pro-
ducing infectious progeny. It is through this pathway that the genes for
cellular transformation are expressed. A latent virus can be reactivated
by various factors, such as excessive exposure to ultraviolet light (in the
case of HSV-1/2 and VZV), endotoxins, plant agglutinins, steroids,
tumor-promoting chemicals, other infections, and increased cytokine
production (as in the case of EBV, HHV-6/7 and, in part, HCMV and
KSHV). Once reactivated, persistent viral activity can be supported by
decreased immune responsiveness resulting from stress or other factors.
Most of these factors can trigger transcriptional activation of the lytic
switch, ORF50/Rta, resulting in a switch from latent to lytic replica-
tion. This pathway leads to the production of infectious virions and the
eventual death of the host cell.
During lytic replication, viral DNA is synthesized as a concatemer
using the “rolling circle” method. Meanwhile, capsid assembly begins
with the formation of a spherical, scaffold-containing procapsid that is
similar to the prohead of bacteriophages.
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Cleavage of scaffolding
proteins by the viral protease results in a stable, angular form called the
B-capsid. The cleaved scaffold proteins are released from the capsid at
the same time that DNA is cleaved to genome length and packaged into
the mature C-capsid. C-capsids ultimately acquire the tegument and
envelope and are released from the cell to begin the infection cycle
again. A third form called the A-capsid is an empty shell resulting from
aberrant processing of DNA and/or scaffold protein. The entire process
by which HSV-1 procapsids mature into angular capsids has been cap-
tured by time-lapse cryo-electron microscopy.
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The procapsid passes
through several continuous intermediate stages of maturation on its
way to becoming an angular, mature capsid (Fig. 2), through sponta-
neous, yet poorly understood, pathways.
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