Viral Genetics

dr. Rizka Ariani, M.Biomed

Departemen Mikrobiologi
Fakultas Kedokteran Universitas Muhammadiyah Sumatera Utara
• Viruses are subject to the same genetic principles at work in other
living systems, namely mutation, selection, complementation, and
recombination

• Genetics impacts all aspects of virology, including the natural

evolution of viruses, clinical management of virus infections, and
experimental virology
Viruses Genetic
Example of multiplication
virus
Fundamental Genetic Concepts
• Genotype refers to the actual genetic change from wild-type in a
particular virus mutant
• Phenotype refers to the measurable manifestation of that change in a
given assay system
• This distinction is emphasized by the fact that a single genotype may
express different phenotypes depending on the assay applied
Fundamental Genetic Concepts
• Selection and screen refer to two fundamentally different methods of
identifying individual virus variants contained in a mixed population
of viruses
• Selection implies that a condition exists where only the desired virus
will grow, and growth of unwanted viruses is suppressed
• Screen implies that both the desired virus variant and one or several
other unwanted virus types grow under a given condition, such that
many viruses must be analyzed individually to identify the desired
variant
Fundamental Genetic Concepts

• The terms essential and nonessential describe phenotypes,

specifically whether a given gene is required for growth under a
specific condition

• Genes that are required for growth under a specific condition are
termed essential, and those that are not required are termed
nonessential
Viral genomes à mutations spontaneously à creating new virus strains

New variants can be identified :

• their nucleotide sequences
• antigenic differences(serotypes)
• differences in functional or structural properties

Mutations in essential genes can inactivate the virus

Mutations in other genes may produce antiviral drug resistance or alter the antigenicity or pathogenicity
of the virus

Errors in copying à viral genome during virus replication à many mutations

This is because of the poor fidelity of the viral polymerase and the rapid rate of genome replication

RNA viruses do not have a genetic error-checking mechanism à the rates of mutation for RNA viruses
are usually greater than for DNA viruses
Interactions among viruses

• two or more virus particles infect the same host cell

• sufficiently closely related à within the same viral family

• Genetic interaction result :

• progeny that are heritably (genetically) different from either parent

• Non-genetic interaction result :

• similar to the parental viruses
Interactions among viruses

1. Recombination
• production of progeny virus àcarries traits not found together in either
parent
• classic mechanism : the nucleic acid strands break à part of genome of
one parent is joined to part of the genome of the second parent
• viruses with segmented genomes (eg, influenza virus) à the formation of
recombinants à caused by reassortment of individual genome fragments
in multiply infected cells rather than by an actual crossover event
Interactions among viruses

2. Complementation

• In cells infected with two viruses, one or both of which may be defective
• replication of one or both under conditions would not ordinarily occur
• The basis for complementation à one virus provides a gene product in
which the second is defective, allowing the second virus to grow
• The genotypes of the two viruses remain unchanged
Interactions among viruses

3. Phenotypic Mixing
• The association of a genotype with a heterologous phenotype
• the genome of one virus becomes randomly incorporated within capsid
proteins specified by a different virus or a capsid consisting of
components of both viruses
• Extreme condition called à “phenotypic masking” or “transcapsidation”
• The nucleocapsid of one virus becomes encased within an envelope
specified by another à a phenomenon designated “pseudotype
formation”
Interactions among viruses

4. Interference
• The effect of infection of one cell with two viruses à leads to an inhibition of
multiplication of one of the viruses
• Mechanism :

• One virus may inhibit the ability of the second to adsorb to the cell à by blocking its
receptors or by destroying its receptors
• One virus may compete with the second for components of the replication apparatus
(eg, polymerase, translation initiation factor)
• The first virus may cause the infected cell to produce an inhibitor (interferon) that
prevents replication of the second virus
Phatomechanism

Recombination Reassortment

Transcapsidation Marker Rescue

 MUTATIONS

Spontaneous Induced

• Both DNA and RNA • used chemical

viruses undergo mutagens are of two
spontaneous mutation types à in vitro and in
• Spontaneous mutation vivo mutagens
rate in RNA viruses >>
DNA viruses
 MUTANT
MUTATION
VIRUSES
 Mutant Viruses

Mutant Genotype
consequence in either a protein coding sequence or in
a control sequence à a transcriptional promoter, a
two basic categories of
replication origin, or a packaging sequence mutation :

Base
Base substitution
deletion/insertion
Base substitution

• Precise replacement of one nucleotide with a different nucleotide in a

nucleic acid sequence
• Classification :
• Silent à causing no change in amino acid sequence of a protein
• missense à causing replacement of the wild-type amino acid with a different
residue
• Nonsense à causing premature translation termination during protein
synthesis
Base deletion and insertion

• Comprise deletion or insertion of one or more nucleotides in a nucleic

acid sequence
• deletion or insertion of multiples of three nucleotides à result in precise
deletion or insertion of one or more amino acids in a protein sequence

• deletions or insertions that do not involve multiples of three nucleotides à

result in a shift in the translational reading frameà premature termination at
some distance downstream of the mutation
 Mutant Viruses

Mutant Phenotype

Lethal Conditional-Lethal
the most useful mutants are those a condition must be found where
that inhibit virus replication by the mutation in question is not
inactivating a virus gene lethal—hence
Conditional-Lethal Classes
• Host range
• Non-sense
• Temperature sensitivity
• Drug resistance and dependence
• Plaque morphology
• Neutralization escape
 Mutant Viruses

Reversion Leakiness

mutation that results in Not all conditionally a quantitative measure

a change from a lethal mutants are of the ability of a
mutant genotype to completely defective in mutant virus to grow
the original wild-type replication under non under non permissive
genotype permissive conditions conditions
Antivirus
• Viruses are obligate intracellular parasites à antiviral agents must be
capable of selectively inhibiting viral functions without damaging the
host à the development of such drugs very difficult
• Limitations making drug treatment relatively ineffective :
• rounds of virus replication occur during the incubation period
• the virus has spread before symptoms appear
Mechanism of antiviral drugs
• Nucleoside and Nucleotide Analogs
• Reverse Transcriptase Inhibitors
• Protease Inhibitors
• Integrase Inhibitors
• Fusion inhibitors
References
• (Lange) Karen C. Carroll, Janet Butel, Stephen Morse-Jawetz Melnick
& Adelbergs Medical Microbiology 27 E-McGraw-Hill Education _
Medical (2015)
• David M. Knipe, Peter Howley-Fields Virology (Knipe, Fields Virology)-
2 Volume Set)-LWW (2013)
• J Flint, V Racaniello, G Rall, A M Skalka-Principles of Virology. 1 - 2-
ASM Press (2015)
• Patrick R. Murray, Ken S. Rosenthal, Michael A. Pfaller-Medical
Microbiology-Elsevier (2015)
THANK YOU