Download General Steps in Viral Replication Cycles

College of Dentistry
Third stage
Asst.Proff. Dina M.R. Alkhafaf
Oral Virology.
Viruses are the smallest infectious agents (ranging from about 20 to
300 nm in diameter) and contain only one kind of nucleic acid (RNA or
DNA) as their genome. The nucleic acid is encased in a protein shell,
which may be surrounded by a lipid-containing membrane. The entire
infectious unit is termed a virion. Viruses are parasites at the genetic
level, replicating only in living cells and are inert in the extracellular
environment. The viral nucleic acid contains information necessary to
cause the infected host cell to synthesize virus-specific macromolecules
required for the production of viral progeny. During the replicative cycle,
numerous copies of viral nucleic acid and coat proteins are produced. The
coat proteins assemble together to form the capsid, which encases and
stabilizes the viral nucleic acid against the extracellular environment and
facilitates the attachment and penetration by the virus upon contact with
new susceptible cells. The virus infection may have little or no effect on
the host cell or may result in cell damage or death. The spectrum of
viruses is rich in diversity. Viruses vary greatly in structure, genome
organization and expression, and strategies of replication and
transmission. The host range for a given virus may be broad or extremely
limited. Viruses are known to infect unicellular organisms, such as
mycoplasmas, bacteria, and algae, and all higher plants and animals.
. Much informati on on virus–host relationships has been obtained from
studies on bacteriophages, the viruses that attack bacteria. Properties of
individual viruses
TERMS AND DEFINITIONS IN VIROLOGY
Indicated viral components are described below:
Capsid: The protein shell, or coat, that encloses the nucleic acid genome.
Capsomeres: Morphologic units seen in the electron microscope on the
surface of icosahedral virus particles. Capsomeres represent clusters of
polypeptides, but the morphologic units do not necessarily correspond to
the chemically defined structural units.
Defective virus: A virus particle that is functionally deficient in some
aspect of replication.
Envelope: A lipid-containing membrane that surrounds some virus
particles. It is acquired during viral maturation
a budding process
through a cellular membrane (see Figure by 29-3). Virus-encoded
glycoproteins are exposed on the surface of the envelope. These
projections are called peplomers.
Nucleocapsid: The protein–nucleic acid complex representing
the packaged form of the viral genome. The term is commonly used in
cases in which the nucleocapsid is a substructure of a more complex virus
particle.
Structural units: The basic protein building blocks of the coat. They are
usually a collection of more than one nonidentical protein subunit. The
structural unit is often referred to as a protomer.
Subunit: A single folded viral polypeptide chain.
Virion: The complete virus particle. In some instances
(eg,
papillomaviruses, picornaviruses), the virion is identical with the
nucleocapsid. In more complex virions (herpesviruses,
orthomyxoviruses), this includes the nucleocapsid plus a surrounding
envelope. This structure, the virion, serves to transfer the viral nucleic
acid from one cell to another
Prions
Prions are infectious particles composed solely of protein with no
detectable nucleic acid. They are highly resistant to inactivation by heat,
formaldehyde, and ultraviolet light that inactivate viruses. The infectious
prion protein is misfolded and able to change the conformation of the
native prion protein which is encoded by a single cellular gene. Prion
diseases, called “transmissible spongiform encephalopathies,” include
scrapie in sheep, mad cow disease in cattle, and kuru and CreutzfeldtJakob disease in humans.
EVOLUTIONARY ORIGIN OF VIRUSES
The origin of viruses is not known. There are profound differences
among the DNA viruses, the RNA viruses, and viruses that use both DNA
and RNA as their genetic material during different stages of their life
cycle. It is possible that different types of agents are of different origins.
Two theories of viral origin can be summarized as follows:
1. Viruses may be derived from DNA or RNA nucleic acid components
of host cells that became able to replicate autonomously and evolve
independently. They resemble genes that have acquired the capacity to
exist independently of the cell. Some viral sequences are related to
portions of cellular genes encoding protein functional domains. It seems
likely that at least some viruses evolved in this fashion.
2. Viruses may be degenerate forms of intracellular parasites. There is no
evidence that viruses evolved from bacteria, although other obligately
intracellular organisms (eg, rickettsiae and chlamydiae) presumably did
so. However, poxviruses are so large and complex that they might
represent evolutionary products of some cellular ancestor
A. Cubic Symmetry
All cubic symmetry observed with animal viruses is of the icosahedral
pattern, the most efficient arrangement for subunits in a closed shell. The
icosahedron has 20 faces (each an equilateral triangle), 12 vertices, and
fivefold, threefold, and twofold axes of rotational symmetry. The vertex
units have five neighbors (pentavalent), and all others have six
(hexavalent).
There are 60 identical subunits on the surface of an icosahedron.
To build a particle size adequate to encapsidate viral genomes, viral shells
are often composed of multiples of 60 structural units. Larger capsid
structures are formed in some cases to accommodate the size of the viral
genome with the association of additional protein subunits. Most viruses
that have icosahedral symmetry do not have an icosahedral shape rather,
the physical appearance
B. Helical Symmetry
In cases of helical symmetry, protein subunits are bound in a periodic
way to the viral nucleic acid, winding it into a helix.
The filamentous viral nucleic acid–protein complex (nucleocapsid) is
then coiled inside a lipid-containing envelope. Thus, as is not the case
with icosahedral structures, there is a regular, periodic interaction
between capsid protein and nucleic acid in viruses with helical symmetry.
It is not possible for “empty” helical particles to form. All known
examples of animal viruses with helical symmetry contain RNA genomes
and, with the exception of rhabdoviruses, have flexible nucleocapsids that
are wound into a ball inside envelopes .
C. Complex Structures
Some virus particles do not exhibit simple cubic or helical symmetry but
are more complicated in structure. For example, poxviruses are brick
shaped, with ridges on the external surface and a core and lateral bodies
inside
CLASSIFICATION OF VIRUSES
Basis of Classification
The following properties have been used as a basis for the classification
of viruses. The amount of information available in each category is not
the same for all viruses. Genome sequencing is now often performed
early in virus identification, and comparisons with databases provide
detailed information on the viral classification, predicted protein
composition, and taxonomic relatedness to other viruses.
1. Virion morphology, including size, shape, type of symmetry, presence
or absence of peplomers, and presence or absence of membranes.
2. Virus genome properties, including type of nucleic acid (DNA or
RNA), size of the genome, strandedness (single or double), whether
linear or circular, sense (positive, negative, ambisense), segments
(number, size), nucleotide sequence, percent GC content, and presence of
special features (repetitive elements, isomerization, 5′-terminal cap, 5′terminal covalently linked protein, 3′-terminal poly(A) tract).
3. Genome organization and replication, including gene order, number
and position of open reading frames, strategy of replication (patterns of
transcription, translation), and cellular sites (accumulation of proteins,
virion assembly, virion release).
4. Virus protein properties, including number, size, amino acid sequence,
modifications (glycosylation, phosphorylation, myristoylation), and
functional activities of structural and nonstructural proteins (transcriptase,
reverse transcriptase, neuraminidase, fusion activities).
5. Antigenic properties, particularly reactions to various antisera.
6. Physicochemical properties of the virion, including molecular mass,
buoyant density, pH stability, thermal stability, and susceptibility to
physical and chemical agents, especially solubilizing agents and
detergents.
7. Biologic properties, including natural host range, mode of
transmission, vector relationships, pathogenicity, tissue tropisms, and
pathology.
General Steps in Viral Replication Cycles
A variety of different viral strategies have evolved for accomplishing
multiplication in parasitized host cells. Although the details vary from
group to group, the general outline of the replication cycles is similar.
The growth cycles of a doublestranded DNA virus and a positive-sense,
single-stranded RNA virus are diagrammed in Figure 29-5. Details are
included in the following chapters devoted to specific virus groups.
A. Attachment, Penetration, and Uncoating
The first step in viral infection is attachment, interaction of a virion with
a specific receptor site on the surface of a cell. Erally glycoproteins. In
some cases, the virus binds protein sequences (eg, picornaviruses) and in
others oligosaccharides (eg, orthomyxoviruses and paramyxoviruses).
The presence or absence of receptors plays an important determining role
in cell tropism and viral pathogenesis. Not all cells in a susceptible host
will express the necessary receptors; for example, poliovirus is able to
attach only to cells in the central nervous system and intestinal tract of
primates. Each susceptible cell may contain up to 100,000 receptor sites
for a given virus. After binding, the virus particle is taken up inside the
cell. This step is referred to as penetration or engulfment. In some
systems, this is accomplished by receptor-mediated endocytosis, with
uptake of the ingested virus particles within endosomes. There are also
examples of direct penetration of virus particles across the plasma
membrane. In other cases, there is fusion of the virion envelope with the
plasma membrane of the cell. Those systems involve the interaction of a
viral fusion protein with a second cellular receptor or coreceptor.
Uncoating occurs concomitantly with or shortly after penetration.
Uncoating is the physical separation of the viral nucleic acid from the
outer structural components of the virion so that it can function. The
genome may be released as free nucleic acid (picornaviruses) or as a
nucleocapsid
(reoviruses).
The
nucleocapsids
usually
contain
polymerases. Uncoating may require acidic pH in the endosome. The
infectivity of the parental virus is lost at the uncoating stage. Viruses are
the only infectious agents for which dissolution of the infecting agent is
an obligatory step in the replicative
B. Expression of Viral Genomes and Synthesis of Viral Components
The synthetic phase of the viral replicative cycle ensues after uncoating
of the viral genome. The essential theme in viral replication is that
specific mRNAs must be transcribed from the viral nucleic acid for
successful expression and duplication of genetic information. After this is
accomplished, viruses use cell components to translate the mRNA.
Various classes of viruses use different pathways to synthesize the
mRNAs depending on the structure of the viral nucleic acid. Table 29-2
summarizes various pathways of transcription (but not necessarily those
of replication) of the nucleic acids of different classes of viruses. Some
viruses (eg, rhabdoviruses) carry RNA polymerases to synthesize
mRNAs. RNA viruses of this type are called negative-strand (negativesense) viruses because their single-strand RNA genome is complementary
to mRNA, which is conventionally designated positive strand (positive
sense). The negative-strand viruses must supply their own RNA
polymerase because eukaryotic cells lack enzymes able to synthesize
mRNA off an RNA template.
In the course of viral replication, all of the virus-specified
macromolecules are synthesized in a highly organized sequence. In some
viral infections, notably those involving double-stranded DNA-containing
viruses, early viral proteins are synthesized soon after infection and late
proteins are made only late in infection after viral DNA synthesis begins.
Early genes may or may not be shut off when late products are made. In
contrast, most, if not all, of the genetic information of RNA-containing
viruses is expressed at the same time. In addition to these temporal
controls, quantitative controls also exist because not all viral proteins are
made in the same amounts. Viral microRNAs or virus-specific proteins
may regulate the extent of transcription of the genome or the
translation of viral mRNA.
C. Morphogenesis and Release
Newly synthesized viral genomes and capsid polypeptides assemble
together to form progeny viruses. Whereas icosahedral capsids can
condense in the absence of nucleic acid, nucleocapsids of viruses with
helical symmetry cannot form without viral RNA. In general,
nonenveloped viruses accumulate in infected cells, and the cells
eventually lyse and release the virus particles.