2. Capsid
-The capsid accounts for most of the virion mass. It is the protein coat
of the virus. It is a complex and highly organized entity which gives form
to the virus. Subunits called protomeres
aggregate to form capsomeres which in turn aggregate to form the capsid.
3. Envelope
-this is an amorphous structure composed of lipid, protein and carbohydrate
which lies to the outside of the capsid. It contains a mosaic of antigens
from the host and the virus. A naked virus is one without an envelope.
4. Spikes.
These are glycoprotein projections which have enzymatic and/or adsorption
and/or hemagglutinating activity. They arise from the envelope and are
highly antigenic.
Morphology
(Symmetry)
1. Icosahedral
-The protomeres aggregate in groups of five or six to form the capsomere.
In electron micrographs, capsomeres are recognized as regularly spaced
rings with a central hole. The shape and dimensions of the icosahedron
depends on characteristics of its protomeres. All icosahedral capsids have
12 corners each occupied by a penton capsomere and 20 triangular faces,
each containing the same number of hexon capsomeres. Icosahedral symmetry
is identical to cubic
symmetry.
From
Jawetz, R., J.L. Melnick, and E.A. Adelberg, Review of Medical Microbiology,
16th Edition, pp. 347, Figure 27-3. Reproduced with permission.
2. Helical
-The protomeres are not grouped in capsomeres, but are bound to each other
so as to form a ribbon-like structure. This structure folds into a helix
because the protomeres are thicker at one end than at the other. The diameter
of the helical capsid is determined by characteristics of its protomeres,
while its length is determined by the length of the nucleic acid it encloses.
From
Jawetz, R., J.L. Melnick, and E.A. Adelberg, Review of Medical Microbiology,
16th Edition, pp. 347, Figure 27-3. Reproduced with permission.
3. Complex
-e.g., that exhibited by poxvirus and rhabdovirus.
This group comprises all those viruses which do not fit into either of
the above two groups.
From
Jawetz, R., J.L. Melnick, and E.A. Adelberg, Review of Medical Microbiology,
16th Edition, pp. 347, Figure 27-3. Reproduced with permission.
Replication
Cycle
1.
Adsorption -Viruses can enter cells via phagocytosis, viropexis or adsorption.
Adsorption is the most common process and the most highly specific process.
It requires the interaction of a unique protein on the surface of the virus
with a highly specific receptor site on the surface of the cell.
2.
Penetration -This occurs by one or more processes.
Enveloped
viruses fuse their envelope with the membrane of the host cell. This involves
local digestion of the viral and cellular membranes, fusion of the membranes
and concomitant release of the nucleocapsid into the cytoplasm.
Naked
viruses bind to receptor sites on the cellular membrane, digest the membrane
and enter into the cytoplasm intact.
Both
naked and enveloped viruses can be ingested by phagocytic cells. However,
in this process they enter the cytoplasm enclosed in a cytoplasmic membrane
derived from the phagocytic cell.
3.
Uncoating -During this stage cellular proteolytic enzymes digest the capsid
away from the nucleic acid. This always occurs in the cytoplasm of the
host cell. The period of the replication cycle between the end of the uncoating
stage and maturation of new viral particles is termed the eclipse.
Thus during the eclipse stage, no complete viral particles can be viewed
within the cell.
4.
Replication of nucleic acid. Replication of viral nucleic acid is a complex
and variable process. The specific process depends on the nucleic acid
type.
From
Jawetz, R., J.L. Melnick, and E.A. Adelberg, Review of Medical Microbiology,
16th Edition, pp. 353, Figure 27-9. Reproduced with permission.
DNA
virus replication -with the exception of the poxviruses, all DNA viruses
replicate in the nucleus. In some cases one of the DNA strands is transcribed
(in others both strands of a small part of the DNA may be transcribed)
(step 4) into specific mRNA, which in turn is translated (step 5) to synthesize
virus-specific proteins such as tumor antigen and enzymes necessary for
biosynthesis of virus DNA. This period encompasses the early virus functions.
Host cell DNA synthesis is temporarily elevated and is then suppressed
as the cell shifts over to the manufacture of viral DNA (step 6). As the
viral DNA continues to be transcribed, late virus functions become apparent.
Messenger RNA transcribed during the later phase of infection (step 6)
migrates to the cytoplasm and is translated (step 7). Proteins for virus
capsids are synthesized and are transported to the nucleus to be incorporated
into the complete virion (step 8).
Assembly
of the protein subunits around the viral DNA results in the formation of
complete virions (step 9), which are released after cell lysis.
The
single-stranded DNA viruses first form a double stranded DNA, utilizing
a host DNA-dependent DNA polymerase. They then undergo a typical replication
cycle.
From
Jawetz, R., J.L. Melnick, and E.A. Adelberg, Review of Medical Microbiology,
16th Edition, pp. 352, Figure 27-8. Reproduced with permission.
RNA
virus replication -with the exception of the orthomyxoviruses and retroviruses,
all RNA viruses replicate in the cytoplasm of the host cell. The exact
process varies with the species of virus. The single-stranded RNA that
is released after uncoating will act as either: (a) the mRNA to synthesize
viral-coded proteins; or (b) a template to synthesize mRNA; or (c) a template
to synthesize double stranded RNA, which is then used as a template to
synthesize mRNA; or (d) a template to synthesize double-stranded DNA, which
is then utilized as a template to synthesize mRNA. This latter process
occurs only with the retroviruses (oncornaviruses).
The
replication of poliovirus, which contains a single-stranded RNA as its
genome, provides a useful example. All of the steps are independent of
host DNA and occur in the cell cytoplasm. Polioviruses absorb to cells
at specific cell receptor sites (step 1), losing in the process one virus
polypeptide. The sites are specific for virus coat-cell interactions. After
attachment, the virus particles are taken into the cell by viropexis
(similar to pinocytosis) (step 2), and the
viral RNA is uncoated (step 3). The single-stranded RNA then serves as
its own messenger RNA. This messenger RNA is translated (step 4), resulting
in the formation of an RNA-dependent RNA polymerase that catalyzes the
production of a replication
intermediate (RI), a partially double-stranded
molecule consisting of a complete RNA strand and numerous partially completed
strands (step 5). At the same time, inhibitors of cellular RNA and protein
synthesis are produced. Synthesis of (+) and (-) strands of RNA occurs
by similar mechanisms. The RI consists of one complete (-) strand and many
small pieces of newly synthesized (+) strand RNA (step 6). The replicative
form (RF) consists of two complete RNA strands,
one (+) and one (-).
The
single (+) strand RNA is made in large amounts and may perform any one
of three functions: (a) serve as messenger RNA for synthesis of structural
proteins; b) serve as template for continued RNA replication; or (c) become
encapsulated, resulting in mature progeny virions. The synthesis of viral
capsid proteins (step 7) is initiated at about the same time as RNA synthesis.
The
entire poliovirus genome acts as its own mRNA, forming a polysome of approximately
350S, and is translated to form a single large polypeptide that is subsequently
cleaved to produce the various viral capsid polypeptides. Thus, the poliovirus
genome serves as a polycistronic messenger molecule. Poliovirus contains
four polypeptides.
5.
Maturation and Release
Naked
viruses -Maturation consists of two main processes: the assembly of the
capsid, and its association with the nucleic acid. Maturation occurs at
the site of nucleic acid replication. After they are assembled into mature
viruses, naked virions may become concentrated in large numbers at the
site of maturation, forming inclusion
bodies. Naked virions are released in different
ways, which depend on the virus and the cell type. Generally, RNA-containing
naked viruses are released rapidly after maturation and there is little
intracellular accumulation; therefore, these viruses do not form predominant
inclusion bodies. On the other hand, DNA-containing naked icosahedral viruses
that mature in the nucleus do not reach the cell surface as rapidly, and
are released when the cells undergo autolysis or in some cases are extruded
without lysis. In either case they tend to accumulate within the infected
cells over a long period of time. Thus, they generally produce highly visible
inclusion bodies.
Enveloped
viruses -In the maturation of enveloped viruses, a capsid must first be
assembled around the nucleic acid to form the nucleocapsid, which is then
surrounded by the envelope. During the assembly of the nucleocapsid, virus-coded
envelope proteins are also synthesized. These migrate to the plasma membrane
(if assembly occurs in the cytoplasm) or to the nuclear membrane (if assembly
occurs in the nucleus) and become incorporated into that membrane. Envelopes
are formed around the nucleocapsids by budding of cellular membranes.
NOTE:
Enveloped viruses will have an antigenic mosaicism characteristic of the
virus and the host cell. Viruses are slowly and continuously released by
the budding process with the results that: (a) the cell is not lysed; and
(b) little intracellular accumulation of virus occurs; and (c) inclusion
bodies are not as evident as with naked viruses.
Complex
viruses -These viruses, of which the poxvirus is a good example, begin
the maturation process by forming multilayered membranes around the DNA.
These layers differentiate into two membranes: The inner one contains the
characteristic nucleoid, while the external one acquires the characteristic
pattern of the surface of the virion.
These
form very characteristic cytoplasmic inclusion bodies. The viruses are
generally released from the cell via cell lysis.
Summary
1.
Viruses contain either DNA or RNA as their genetic material, but not both.
This nucleic acid usually has unique chemical and/or physical features
which makes it distinguishable from human nucleic acid.
2.
Viral nucleic acid is enclosed in a capsid made up of protein subunits
called protomeres.
3.
Some species of viruses have a membrane, the envelope, surrounding the
capsid; other species do not have an envelope, i.e., they are naked. Enveloped
viruses have glyco-protein spikes arising from their envelope. These spikes
have enzymatic, absorptive, hemagglutinating and/or antigenic activity.
4.
The morphology of a virus is determined by the arrangement of the protomeres.
When protomeres aggregate into units of five or six (capsomeres) and then
condense to form a geometric figure having 20 equal triangular faces and
12 apices, the virus is said to have icosahedral (cubic) morphology. When
protomeres aggregate to form a capped tube, they are said to have helical
morphology. Any other arrangement of the protomeres results in a complex
morphology.
5.
All viruses undergo a replication cycle in their human host cell consisting
of adsorption, penetration, uncoating, nucleic acid replication, maturation
and release stages.
6.
During the viral replication cycle, an accumulation of mature viruses,
incomplete viruses and viral parts occurs within the cell. This accumulation
is the inclusion body.
The size, shape, location and chemical properties of the inclusion body
are used by the pathologist to diagnose viral infectious disease.
7.
A virally-infected cell generally presents three signals that it is infected.
The first is the production of double-stranded RNA, which induces interferon;
the second is the expression of viral protein on the surface of the plasma
membrane, thus causing activation of cytotoxic T-cells, natural killer
cells and sometimes induction of antibody synthesis. The third is the formation
of an inclusion body either within the cytoplasm or the nucleus or very
rarely within both the cytoplasm and nucleus.
8.
In general, all DNA-containing viruses replicate in the host cell nucleus.
The exceptions to the rule are the poxviruses.
9.
In general, all RNA-containing viruses replicate in the host cell cytoplasm.
The exceptions to the rule are the retroviruses and the orthomyxoviruses.
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