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Viral replication is the term used by virologists to describe the formation of biological viruses
during the infection process in the target host cells. Viruses must first get into the cell
before viral replication can occur. From the perspective of the virus, the purpose of viral
replication is to allow production and survival of its kind. By generating abundant copies
of its genome and packaging these copies into viruses, the virus is able to continue
infecting new hosts. Replication between viruses is greatly varied and depends on the
type of genes involved. Viral populations do not grow through cell division, because they
are acellular; instead, they use the machinery and metabolism of a host cell to produce
multiple copies of themselves, and they assemble in the cell.
The life cycle of viruses differs greatly between species but there are six basic stages in the life
cycle of viruses:
Attachment is a specific binding between viral capsid proteins and specific receptors on
the host cellular surface. This specificity determines the host range of a virus. For
example, HIV infects only human T cells, because its surface protein, gp120, can interact
with CD4 and receptors on the T cell's surface. This mechanism has evolved to favour
those viruses that only infect cells in which they are capable of replication. Attachment to
the receptor can induce the viral-envelope protein to undergo changes that results in the
fusion of viral and cellular membranes.
Penetration follows attachment; viruses enter the host cell through receptor mediated
endocytosis or membrane fusion. This is often called viral entry. The infection of plant
cells is different from that of animal cells. Plants have a rigid cell wall made of cellulose
and viruses can only get inside the cells after trauma to the cell wall. Viruses such as
tobacco mosaic virus can also move directly in plants, from cell to cell, through pores
called plasmodesmata.[83] Bacteria, like plants, have strong cell walls that a virus must
breach to infect the cell. Some viruses have evolved mechanisms that inject their genome
into the bacterial cell while the viral capsid remains outside.
Uncoating is a process in which the viral capsid is degraded by viral enzymes or host
enzymes thus releasing the viral genomic nucleic acid.
Replication involves synthesis of viral messenger RNA (mRNA) for viruses except
positive sense RNA viruses (see above), viral protein synthesis and assembly of viral
proteins and viral genome replication.
Following the assembly of the virus particles, post-translational modification of the viral
proteins often occurs. In viruses such as HIV, this modification (sometimes called
maturation) occurs after the virus has been released from the host cell.
Viruses are released from the host cell by lysisa process that kills the cell by bursting
its membrane. Enveloped viruses (e.g., HIV) typically are released from the host cell by
budding. During this process the virus acquires its envelope, which is a modified piece of
the host's plasma membrane.
SMB 301:
Lecturer:
INTRO TO VIROLOGY
KU-MAIN CAMPUS
Shem Peter Mutua Mutuiri smutuiri@gmail.com
BSc. MICROBIOLOGY
Protein synthesis
Proteins are essential to life. Cells produce new protein molecules from amino acid
building blocks based on information coded in DNA. Each type of protein is a specialist
that only performs one function, so if a cell needs to do something new, it must make a
new protein. Viruses force the cell to make new proteins that the cell does not need, but
are needed for the virus to reproduce. Protein synthesis basically consists of two major
steps: transcription and translation.
Transcription is the process where information in DNA, called the genetic code, is used
to produce RNA copies called messenger RNA (mRNA). These migrate through the cell
and carry the code to ribosomes where it is used to make proteins. This is called
translation because the protein's amino acid structure is determined by the mRNA's code.
Some RNA genes of viruses function directly as mRNA without further modification. For
this reason, these viruses are called positive-sense RNA viruses. In other RNA viruses,
the RNA is a complementary copy of mRNA and these viruses rely on the cell's or their
own enzyme to make mRNA. These are called negative-sense RNA viruses. In viruses
made from DNA, the method of mRNA production is similar to that of the cell. The
species of viruses called retroviruses behave completely differently: they have RNA, but
inside the host cell a DNA copy of their RNA is made. This DNA is then incorporated
into the host's, and copied into mRNA by the cell's normal pathways.
The genetic material within viruses, and the method by which the material is replicated, vary
between different types of viruses.
DNA viruses
The genome replication of most DNA viruses takes place in the cell's nucleus. If the cell
has the appropriate receptor on its surface, these viruses enter the cell by fusion with the
cell membrane or by endocytosis. Most DNA viruses are entirely dependent on the host
cell's DNA and RNA synthesising machinery, and RNA processing machinery. The viral
genome must cross the cell's nuclear membrane to access this machinery.
RNA viruses
These viruses are unique because their genetic information is encoded in RNA.
Replication usually takes place in the cytoplasm. RNA viruses can be placed into about
four different groups depending on their modes of replication. The polarity (whether or
not it can be used directly to make proteins) of the RNA largely determines the replicative
mechanism, and whether the genetic material is single-stranded or double-stranded. RNA
viruses use their own RNA replicase enzymes to create copies of their genomes.
Reverse transcribing viruses
These replicate using reverse transcription, which is the formation of DNA from an RNA
template. Reverse transcribing viruses containing RNA genomes use a DNA intermediate
to replicate, whereas those containing DNA genomes use an RNA intermediate during
genome replication. Both types use the reverse transcriptase enzyme to carry out the
nucleic acid conversion. Retroviruses often integrate the DNA produced by reverse
transcription into the host genome. They are susceptible to antiviral drugs that inhibit the
reverse transcriptase enzyme, e.g. zidovudine and lamivudine. An example of the first
type is HIV, which is a retrovirus. Examples of the second type are the Hepadnaviridae,
which includes Hepatitis B virus.
SMB 301:
Lecturer:
INTRO TO VIROLOGY
KU-MAIN CAMPUS
Shem Peter Mutua Mutuiri smutuiri@gmail.com
BSc. MICROBIOLOGY
SMB 301:
Lecturer:
INTRO TO VIROLOGY
KU-MAIN CAMPUS
Shem Peter Mutua Mutuiri smutuiri@gmail.com
BSc. MICROBIOLOGY
Viruses with polycistronic mRNA where the genome RNA forms the mRNA and is
translated into a polyprotein product that is subsequently cleaved to form the mature
proteins. This means that the gene can utilize a few methods in which to produce proteins
from the same strand of RNA, all in the sake of reducing the size of its gene.
Viruses with complex transcription, for which subgenomic mRNAs, ribosomal
frameshifting and proteolytic processing of polyproteins may be used. All of which are
different mechanisms with which to produce proteins from the same strand of RNA.
Examples of this class include the families Coronaviridae, Flaviviridae and Picornaviridae.
Class 5: Single stranded RNA viruses - Negative (-) sense
The negative sense RNA viruses and indeed all genes defined as negative sense cannot be
directly accessed by host polymerases to immediately form proteins. Instead, they must be
SMB 301:
Lecturer:
INTRO TO VIROLOGY
KU-MAIN CAMPUS
Shem Peter Mutua Mutuiri smutuiri@gmail.com
BSc. MICROBIOLOGY
transcribed by viral polymerases into a "readable" form, which is the positive sense reciprocal.
These can also be divided into two groups:
Viruses containing non segmented genomes for which the first step in replication is
transcription from the (-) stranded genome by the viral RNA-dependent RNA polymerase
to yield monocistronic mRNAs that code for the various viral proteins. A (+) sense
genome copy is then produced that serves as template for production of the (-) strand
genome. Replication is within the cytoplasm.
Viruses with segmented genomes for which replication occurs in the nucleus and for
which the viral RNA-dependent RNA polymerase produces monocistronic mRNAs from
each genome segment. The largest difference between the two is the location of
replication.
SMB 301:
Lecturer:
INTRO TO VIROLOGY
KU-MAIN CAMPUS
Shem Peter Mutua Mutuiri smutuiri@gmail.com
BSc. MICROBIOLOGY
SMB 301:
Lecturer:
INTRO TO VIROLOGY
KU-MAIN CAMPUS
Shem Peter Mutua Mutuiri smutuiri@gmail.com
BSc. MICROBIOLOGY
SUMMARY
INTRO TO VIROLOGY
KU-MAIN CAMPUS
Shem Peter Mutua Mutuiri smutuiri@gmail.com
BSc. MICROBIOLOGY