Lecture 2 BSCI437. VIRAL
GENOMES, PROTEINS, AND
Criteria for viral genomes
• Must use same genetic code as
• Must use same biomolecules as
host: Nucleic Acids. Proteins,
carbohydrates and lipids.
• Modifications (polyadenylation of
mRNA, capping, splicing) must
either depend on viral enzymes or
• Continuous pressure to minimize
• Fast replication (especially
important in bacteria where virus
must keep up with host)
• Genome packaging.
– It takes a capsid of several million
Daltons to package a 10 kb genome.
– The larger the genome the larger
the capsid must be and this means
more energy and time required for
All varieties of
– (+) ssRNA
– (-) ssRNA
– retrovirus (+ssRNA dsDNA)
– Mixed DNA and RNA
Tautomerization of pyramidines:
the primary chemical basis for mutagenesis.
Tautomerization of pyramidines:
Cytosine tautomerization is an order of
Properties of viruses
relative to genome type
• Size Range: Range from encoding
as little ≈2 kb (Circoviruses), to
as large as 800 kb (Mimiviruses)
• Variations (single molecule or
• NTP Polymerases: Viral or host
• Fidelity of replication
– From high fidelity (<10-9
/nt) to low
Includes every possible
• double stranded or single
• linear or circular,
• contiguous, segmented, or
• polarity: Single stranded (+)
strand, (-) strand, or
Structure & Composition of
Genomes: Generally, any and all
possible combinations are known.
Composition. Can be RNA,
DNA, and/or any
•DNA or RNA
•DNA with short RNA
•DNA or RNA with
covalently attached protein
• Terminal Redundancy:
genomes of many viruses are
terminally redundant. Used
as tools for replication,
expression, integration into
host chromosomes, and for
protection of ends.
Examples include λ, retro-,
adeno-, parvo-, pox-, bunya-,
• Covalent Modifications:
Includes modifications to
nucleic acids (eg.
pseudouridylation, etc.), and
covalent linkage with
proteins. Of the latter,
proteins covalently linked to
the 5' ends of picorna- and
adenoviruse RNAs play
important roles in cap-
• Hijack host proteins for some or
all replication functions
• Overlapping genes
• Genes on both strands of dsDNA
in opposite directions
• Multiple splicing of the same
transcript to make many
different proteins (only need 1
• Polyprotein production from one
mRNA and subsequent proteolytic
• Frameshift mechanisms allow
downstream out of frame genes
to be made at appropriate
Viral adaptation and
evolution through mutation
• Three major phenomena are
1. Base misincorporations by
2. Recombination by breakage
and religation in all DNA
viruses or RNA viruses with a
DNA intermediate or by Copy-
choice with many ssRNA
3. Reassortment in the case of
viruses with multipartite
genomes (more than one
• Viruses are subject to the same type
of mutations as other organisms:
– Transitions and transversions
– Nonsense mutations.
• Mutations can be spontaneous or
– Inducing agents commonly used to directly
mutate the virus for study.
– Mutations can be used to map genes in
viruses just as they are used to map in
• Mutations are also useful in
determining the function of a protein.
– Conditional mutants- a mutant phenotype
that is replication competent under
“permissive” but not “restrictive” or
• Mutations are subject to reversion
either at the same or a different
(pseudorevertant) location in the
• Mutants can also be complemented by
other viral strains in a superinfection.
• Reassortment: exchange of
genome segments in
segmented viruses. e.g.
• Transduction: Incorporation
of host cellular genes into
viral genome, e.g. RSV
• Attenuation: virulence lost
but virus can still replicate in
• Recombination: Exchange of
genetic information between
two or more virus genomes.
• Interference: inhibition of
replication or infection of
one type of virus by another.
e.g. HIV-1 prevention of CD4
expression in infected cell;
Particles in plant viruses.
• Phenotypic mixing: exchange
of envelopes or coat proteins
between different viruses.
As few as 2 and as many as >50 virus-
encoded proteins. Generally divided into
“Structural” and “Non-structural”.
• Structural: These compose the
capsids/nucleocapsids, and envelope
– Primary function of those involved in
capsid/nucleocapsids is to serve as
building blocks for the virion (viral particle).
• Envelope proteins are typically
glycoproteins in the form of spikes or
– Typically, these serve as receptors for host
cell-surface glycoproteins and are involved in
viral attachment and entry into cells
• Non-structural: proteins with enzymatic,
virus replicative, or for interactions with
host-cell encoded factors.
– Examples from HIV include Pol, Int, RNase H,
Integrase, Nef, Vif, and Tat.
• Viral envelopes contain
complex mixtures of neutral
lipids, phospholipids and
• As a rule, their composition
resembles that of the host cell
membrane from which the
envelope was derived.
• Viruses can pick up molecules
from host cells.
– Make up bulk of viral envelopes.
– Taken from host cellular
– tRNAs used for priming.
– 5S rRNA and other trans-
acting factors used in