VOVED

At their simplest, viruses can be viewed as protein packages

transmitting foreign nucleic acid between host cells.
Th e type of nucleic acid present depends on the virus concerned. All viruses contain one or more molecules of
either RNA or DNA, but not both. Th ey can, therefore, be
defi ned as RNA or DNA viruses . Most RNA viruses contain
single-stranded RNA ( ssRNA ), but some viruses contain
double-stranded RNA ( dsRNA ). If the base sequence
of the RNA strand is identical to viral mRNA, it is called
the positive (+) strand. If it is complementary, it is called
the negative (−) strand. Most DNA viruses contain double-
stranded DNA ( dsDNA ), but a small number contain
single-stranded DNA ( ssDNA ). Th e size of the nucleic acid
varies widely, with the smallest viral genomes coding for
3–4 proteins and the largest coding for over 100 proteins.
Th e viral nucleic acid is contained and protected
within a protein coat called the capsid . Capsids are usually
made up of protein subunits called protomers which
are generated in the host cell and can interact spontaneously
to form the capsid in a process called self-assembly .
Once the capsid contains the viral nucleic acid, the whole
assembly is known as the nucleocapsid . In some viruses,
the nucleocapsid may contain viral enzymes which are
crucial to its replication in the host cell. For example,
the fl u virus contains an enzyme called RNA-dependent
RNA polymerase within its nucleocapsid ( Fig. 20.1 ).
Additional membranous layers of carbohydrates and
lipids may surround the nucleocapsid, depending on the
virus concerned. Th ese are usually derived from the host
cell, but they may also contain viral proteins which have
been coded by viral genes.
Th e complete structure is known as a virion and this
is the form that the virus takes when it is outside the
host cell. Th e size of a virion can vary from 10 nm to
400 nm.

ДНА ВИРУСИ
Most DNA viruses contain
double-stranded DNA as their genome and thus can
replicate using host cell machinery to produce mRNA
directly. Papillomavirus, adenovirus, and herpesvirus
are replicated in the host nucleus, and thus use transcriptional
enzymes of the host (i.e., DNA-dependent
RNA polymerase) to synthesize mRNA. This mRNA is
then translated to form proteins needed by the virus,
including enzymes (e.g., DNA-dependent DNA polymerase)
used to produce progeny DNA copies.

РНА ВИРУСИ
Compared to DNA viruses, those viruses with RNA-based
genomes have evolved a wide variety of reproductive strategies.
The single-stranded RNA viruses may be divided
into three groups that differ in the method by which
the RNA genome is utilized. In all three groups, the
RNA genome must serve two functions: to be translated
to form protein and to be replicated to form progeny
RNA strands.
................................

ЖИВОТЕН ЦИКЛУС
Th e various stages involved in the life cycle of a virus are
as follows ( Fig. 20.2 ).
• Adsorption : a virion has to fi rst bind to the outer surface
of a host cell. Th is involves a specifi c molecule on
the outer surface of the virion binding to a specifi c
protein or carbohydrate present in the host cell membrane.
Th e relevant molecule on the host cell can thus
be viewed as a ‘receptor’ for the virion. Of course, the
host cell has not produced this molecule to be a viral
receptor. Th e molecules concerned are usually glycoproteins
which have crucial cellular functions, such as
the binding of hormones. However, the virion takes
advantage of these, and once it is bound, the next stage
can take place—introduction of the viral nucleic acid
into the host cell.
• Penetration and uncoating : diff erent viruses introduce (одвиткување)
their nucleic acid into the host cell by diff erent
methods. Some inject their nucleic acid through the
cell membrane; others enter the cell intact and are
then uncoated. Th is can also happen in a variety of
ways. Th e viral envelope of some virions fuses with the
plasma membrane and the nucleocapsid is then introduced
into the cell ( Fig. 20.2 ). Other virions are taken
into the cell by endocytosis where the cell membrane
wraps itself round the virion and is then pinched off to
produce a vesicle called an endosome (see for example
Fig. 20.40 ). Th ese vesicles then fuse with lysosomes ,
and host cell enzymes aid the virus in the uncoating
process. Low endosomal pH also triggers uncoating. In
some cases, the viral envelope fuses with the lysosome
membrane and the nucleocapsid is released into the
cell. Whatever the process, the end result is the release
of viral nucleic acid into the cell.
• Replication and transcription : viral genes can be
defi ned as early or late. Early genes take over the host
cell such that viral DNA and/or RNA is synthesized.
Th e mechanism involved varies from virus to virus.
For example, viruses containing negative ssRNA use
a viral enzyme called RNA-dependent RNA polymerase
(or transcriptase) to synthesize mRNA which then
codes for viral proteins.
• Synthesis and assembly of nucleocapsids : late genes
direct the synthesis of capsid proteins and these selfassemble
to form the capsid. Viral nucleic acid is then
taken into the capsid to form the nucleocapsid.

Virion release : naked virions (those with no outer layers

round the nucleocapsid) are released by cell lysis
where the cell is destroyed. In contrast, viruses with
envelopes are usually released by a process known
as budding ( Fig. 20.2 ). Viral proteins are fi rst incorporated
into the host cell’s plasma membrane. Th e
nucleocapsid then binds to the inner surface of the cell
membrane and, at the same time, viral proteins collect
at the site and host cell proteins are excluded. Th e
plasma membrane containing the viral proteins then
wraps itself round the nucleocapsid and is pinched off
from the cell to release the mature virion.

АЦИКЛОВИР

Ganciclovir ( Fig. 20.5 ) is an analogue of aciclovir and

bears an extra hydroxymethylene group; valganciclovir
acts as a prodrug for this compound. Penciclovir and its
prodrug famciclovir ( Fig. 20.6 ) are analogues of ganciclovir.
In famciclovir, the two alcohol groups of penciclovir
are masked as esters making the structure less polar,
resulting in better absorption. Once absorbed, the acetyl
groups are hydrolysed by esterases and the purine ring
is oxidized by aldehyde oxidase in the liver to generate
penciclovir. Phosphorylation reactions then take place in
virally infected cells, as described previously.