Viral Genetics and Replication 2

Viruses are simple creatures, lacking an
energy-generating system and having very Viral genetics

limited biosynthetic capabilities. The smallest
viruses have only a few genes; the largest
viruses have as many as 200. Genetically,
viruses have many features in common with
cells, e.g. viruses are subject to mutations,
the genomes of different viruses can
recombine to novel progeny, the expression
of the viral genome can be regulated, and
viral gene products can interact.
An enormous variety of genomic structures
are among viral species; as a group, they
contain more structural genomic diversity
than plants, animals, & other microbes. There
are millions of different types of viruses, but
only about 5,000 types are described in detail.
As of 2015, Virus genome database has more
than 75,000 complete genome sequences.
A virus has either a DNA or RNA
genome & accordingly called DNA virus or Viral genetics
an RNA virus. The vast majority of viruses
have RNA genomes.
Viral genomes are circular, as in the
polyomaviruses, or linear, as in the
adenoviruses. Among RNA viruses and
certain DNA viruses, the genome is often
divided into separate parts called segmented.
For RNA viruses, each segment often codes
for only one protein and they are usually
found together in one capsid.
viral genome, irrespective of nucleic acid
type, is almost always either single-stranded
or double-stranded. Single-stranded
genomes consist of an unpaired nucleic acid.
Double-stranded genomes consist of two
complementary paired nucleic acids.
The virus particles of some virus families,
such as those belonging to the Hepadnaviridae Viral genetics
, contain a genome that is partially double-
stranded and partially single-stranded.
For most viruses with RNA genomes and
some with single-stranded DNA genomes, the
single strands are said to be either
positive-sense (called the plus-strand) or
negative-sense (called the minus-strand),
depending on if they are complementary to the
viral messenger RNA (mRNA). Positive-sense
viral RNA is in the same sense as viral mRNA
and thus at least a part of it can be
immediately translated by the host cell.
Negative-sense viral RNA is complementary
to mRNA and thus must be converted to
positive-sense RNA by an
RNA-dependent RNA polymerase before
translation.
DNA nomenclature for viruses with
single-sense genomic ssDNA is similar to Viral genetics
RNA nomenclature, in that positive-strand
viral ssDNA is identical in sequence to the
viral mRNA and is thus a coding strand, while
negative-strand viral ssDNA is complementary
to the viral mRNA and is thus a template
strand.
Genome size
Genome size varies greatly between
viruses. The smallest viral genomes—the
ssDNA circoviruses, family Circoviridae—
code for only two proteins and have a genome
size of only two kilobases; the largest—the
pandoraviruses—have genome sizes of around
two megabases which code for about 2500
proteins. Virus genes rarely have introns and
often are arranged in the genome so that they
overlap.
Primary structure consists of a linear sequence of nucleotides that are linked together by
phosphodiester bonds. It is this linear sequence of nucleotides that make up the Primary structure
of DNA or RNA. Nucleotides consist of 3 components:
Nitrogenous base ; Adenine, Guanine,Cytosine,Thymine (present in DNA only),Uracil (present in RNA
only)
5-carbon sugar which is called deoxyribose (found in DNA) and ribose (found in RNA).
One or more phosphate groups
Basic structure of
Basic arrangement of nucleotide
nucleotides in DNA
Terms in viral genetics
• Genotype: is the genetic constituent of an organism
• Phenotype: are the observable properties of an organism, which are produced
by the genotype in cooperation with the environment.
• Mutation: is a heritable change in the genotype.
• Genome: is the sum of genes of an organism.
• Wild-type virus: is the original virus from which mutants are derived and with
which the mutants are compared.
• Primary virus isolate: virus isolates from the natural host.
• Defective virus (DV): A defective virus is one that lacks one or more functional
gene required for viral replication. Thus DV required helper activity from
another virus for its replication, e.g. Hepatitis D virus.
• Interfering virus particle (IDPs) : It requires infection by homologous virus as
helper for replication, & interfere with the multiplication of that homologous
virus. Interference probably result from competition by DIPs.
• Pseudovirion: different types of DIPs that contain only host cell DNA rather
than viral genome. DIPs can not replicate.
Interaction among viruses
• Interactions among viruses: When two or more viruses infect the same host
cell. They may interact in a variety of ways (genetics and non-genetic
interaction).
• Recombination: Recombination results in the production of progeny virus
(recombinant) that is different from either parent (genetic reassortment).
• Genetic reactivation: This phenomenon represent special cases of
recombination.
• Marker rescue: recombination between inactivated virus particle & active
virion that produce viable progeny, which is genetically stable.
• Multiplicity reactivation: recombination between inactive virus particles
produce viable genome, which is genetically stable.
• Complementation: Viral gene products of one or two defective viruses.
• Phenotypic mixing: complementation of genotype with heterologous
phenotype.
• Interference: Counteraction between viruses.
Viral replication (Viral
life cycle)
Viruses have evolved different strategies for multiplication in infected
host cells, however, the general outline of replication cycle is similar.
General steps in viral replication

1. Viral attachment
2. Viral penetration
3. Viral Uncoating
4. Transcription of viral genome
5. Translation ad synthesis of viral proteins.
6. Morphogenesis and release.
1.Viral attachment:
This s the first step in viral infection, which include the interaction of a virion with a
specific receptor site on the surface of susceptible cells. Receptors different for
different viruses, but are generally glycoproteins (e.g. HIV to CD4 receptor).
The presence or absence of receptors plays an important role for determination of
cell tropism and viral pathogenesis (e.g. polio viruses attached to cells n Central
nervous system and intestinal tract only).
One attachment occur, an irreversible changes in the virion started.
Viral replication (Viral life cycle)
2. Penetration:
Viral particles are taken up inside the cells.
3. Uncoating:
The physical separation of viral nucleic acid from the outer structural components of the virion.
It occurs at the time or shortly after penetration.
The viral genome may be released as free nucleic acid ( e.g. Picornaviruses)or as
nucleocapsid( Reo viruses).
4.Transcription of viral genome:
Transcription of specific mRNA from viral nucleic acid for successful duplication of genetic
information. Once this occurs the virus use the cellular components to translate the mRNA.
Different viruses use different strategies for synthesis of mRNA depending on the type of nucleic
acid.
The extent to which virus-specific enzymes (sometimes cellular enzymes) are involved in this
process varies from virus to virus.
The intracellular sites of transcription depend on the type of viral genome. All DNA viruses
replicate in the nucleus except Pox virus, and all RNA viruses replicate in the cytoplasm
except Retroviruses and orthomyxoviruses. Viral protein synthesis occurs in the cytoplasm.
Viral replication (Viral life cycle)
:Translation.5
Translation of viral mRNA for protein synthesis in the
.cytoplasmic ribosomes
:Morphogenesis and release.6
The newly synthesized viral genome and capsid protein
are assembled together to form progeny virus. In no-
enveloped viruses the host cell ruptured and the
viruses released. While enveloped viruses released by
budding from cell membrane (cytoplasmic replication)
or nuclear membrane (nuclear replication).
Acute, Latent and chronic infections
Acute viral infection: When the virus enter the body, replicate in
the susceptible cells and produce its disease (intense signs &
symptoms). Then the virus eliminated completely from the body
(Complete recovery).e.g. Hepatitis A virus
In chronic viral infections (e.g. Hepatitis B virus) the virus enter the
host cell and replicate at low levels for unknown period, it may
or may not associated with mild clinical signs. Chronic viral
infections could be chronic persistent or chronic active.
Latent infection occurs when the virus enter the host cell and
remained dormant (Non- active state, non-replicating) for
unknown period and it may reactivate at any time in the life
(Herpes simplex virus-1, Varicella-Zoster).

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Viruses are simple creatures, lacking an

energy-generating system and having very Viral genetics

General steps in viral replication

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