University of Balamand

Faculty of Medicine and

Medical Sciences

CVIR401
Lecture#1 (Part#1)
Viral Biology and Pathogenesis

Instructor: Samer Bazzi, PhD

Definition of a virus

- A virus is an infectious, obligate intracellular parasite composed of a genetic

material (DNA or RNA) that is surrounded by a protein coat and sometimes an
envelope

- A virus is an organism with 2 phases:

Outside the host cell Inside the host cell
Virion
(infectious viral particle)
Properties of viruses

- Viruses range in size 20 – 500 nm in diameter

- Viruses infect all major groups of organisms (from vertebrates, plants to bacteria)
- Some viruses have broader host range than others
Factors affecting host range
i- Ability to get into host cells; if yes
ii- Presence of appropriate cellular machinery to allow
virus replication; if yes
iii- Ability of the virus to get out of cell and spread
infection
Basic components of a virus particle
A- Genome
- Viral genes are encoded in either DNA or RNA molecules
- A single copy of the genome (haploid) is present in all viruses except for the
retrovirus family whose members have 2 copies (diploid)

DNA Genome
- Can be single-stranded (ss) or double-stranded (ds)
- Can be linear or circular
- Always monopartite/non-segmented (all viral genes contained in a single molecule
of nucleic acid)

RNA Genome
- Can be single-stranded (ss) or double-stranded (ds)
- Can be linear or circular
- Can be monopartite/non-segmented or multipartite/segmented (viral genes
distributed in multiple molecules or segments of nucleic acid)
- Positive-sense RNA (coding strand) = (+)RNA (can be used itself as mRNA)
- Negative-sense RNA (template strand) = (−)RNA (complementary to mRNA)
• Cannot be used as mRNA
• Requires virion-associated RNA-dependent RNA polymerase (as part of the
mature virus)
Basic components of a virus particle
B- Capsid
- Protein coat surrounding the viral genome

- Confers protection to the nucleic acid against environment

- Acts as a delivery system for transferring the viral genome from one cell to another

- Functions in receptor recognition - targeting a virus to a susceptible host and cell type

- Made up of subunits of capsomeres

- Capsomeres = clusters of protomers structural units

forming morphological units on the surface of virus particles

DNA or RNA + Capsid structural proteins = Nucleocapsid

(capsomeres, etc.)

- Capsids fall into 3 main morphological/structural groups with

different symmetries
Basic components of a virus particle
B- Capsid

Icosahedral structure

- All faces of icosahedron are identical

- The size of icosahedron depends on:
- size of the encoded capsid proteins
- number of capsomeres (there are always 12 pentons but the number of hexons can
vary considerably).
Basic components of a virus particle
B- Capsid
Helical structure
- Protein subunits interact with each other and
with the nucleic acid to form a coiled, ribbon-like
structure (i.e. influenza virus, rabies virus)

- The length of the helix is determined by length

of viral nucleic acid

- The helix may be rod-like and inflexible (i.e.

Tobacco mosaic virus) or very flexible (i.e.
Paramyxovirus)

- All RNA viruses with helical capsid symmetry

and capable of infecting humans are enveloped

Complex structure

- Oval, brick, or cone-shaped nucleocapsid

- Poxviruses and some retroviruses

Basic components of a virus particle
C- Lipid envelope (present only in some
viruses)

- Derived from a host cell by budding

through plasma membrane, golgi bodies,
or nucleus

- Consists of lipid bilayer and cellular

proteins plus at least 1 virally-encoded
protein involved in the attachment to cells

- Enveloped viruses are infectious only if

the envelope is intact
Basic components of a virus particle
D- Viral proteins:

- Surface proteins (capsid proteins in naked viruses or envelope proteins in

enveloped viruses) perform the following functions:
a) mediate attachment to cell receptors (contribute to species and organ
specificity)
b) induce neutralizing antibodies and CTLs
c) act as targets of antibodies to prevent virus entry and replication
d) determine virus serotype

- Viral structural polypeptides (capsid proteins) are packaged within the virion

- Viral non-structural polypeptides are produced in the infected cell and are not
usually packaged within the virion.

- Viral non-structural polypeptides are important for expression of viral genome

Important Virus Related Terms

Virus isolate: virus that was isolated from an infected host and propagated in culture
Examples on virus isolates names:
BetaCoV/Wuhan/WIV04/2019 SARS-CoV-2 is virus
genus/city of origin/isolate number/year of isolation name NOT isolate name

A/chicken/Vietnam/NCVD-404/2010 (H5N1)
antigenic type of virus/host of origin if other than human/geographical origin/serial
number/all 4 digits or last 2 digits of year of isolation (hemagglutinin subtype and
neuraminidase subtype)

Virus variant: virus whose genome sequence differs from that of a reference virus
(variants of concern)

Virus strain: a variant that possesses unique and stable phenotypic characteristics

Virus serotype: a term used to describe viruses of the same species that are
antigenically different

Human virome: collection of all viruses that are present in or on human (including
eukaryotic and prokaryotic viruses)
Nomenclature of Viruses

- The highest taxonomic group among viruses is the family; families are named with a suffix-viridae.
Subfamilies have the suffix-virinae; genera the suffix-virus

Viruses are named according to their:

- Replication Mode: i.e. Retrovirus; reverse transcribe its RNA genome

- Morphology/Structure: i.e. Coronavirus; crown or appearance of the envelope glycoproteins

i.e. Picornavirus; small RNA virus

- Geographical Region of Discovery/First Isolation: i.e. Ebola virus; village near Ebola river
i.e. Zika virus; Zika forest

- Mode of Transmission: i.e. Arbovirus; arthropod-borne-virus

- Target Organ: i.e. Enterovirus; infects the gut/intestine (enteric: related to or affecting intestine)
i.e. Rhinovirus; infects the nose (rhino: relating to the nose)
 Classification of Viruses
Primary characteristics used in classification:
RNA or DNA
Single-stranded or double-stranded
Linear or circular
NUCLEIC ACID
Non-segmented or segmented (RNA)
Can genome function as mRNA ?
Is genome diploid ?
Capsid Symmetry
VIRION STRUCTURE Envelop absent or present
Number of capsomeres

Secondary characteristics used in classification:

Baltimore classification

Replication strategy
Nucleic acid content
mRNA production strategy
 DNA Viruses
Icosahedral Complex

Enveloped Naked Enveloped

ds ss ds ds

Herpesvirus Parvovirus Papillomavirus Poxvirus

Hepadnavirus Polyomavirus
Adenovirus

Important notes about DNA viruses

- Are double-stranded (ds) except for parvovirus which is single-stranded (ss)
- Have linear genomes except for papilloma and polyoma and hepadna viruses which
have circular genome
- No DNA virus infecting humans has a helical capsid symmetry
 DNA Viruses

Enveloped DNA Viruses Naked DNA Viruses

Mnemonic to help you remember the names of DNA viruses

Pardon Papa As He Has Pox

Parvovirus Poxvirus

Adenovirus Herpesvirus
Papillomavirus
Polyomavirus Hepadnavirus
 RNA Viruses
Icosahedral Helical Complex
Enveloped
Enveloped Naked Enveloped
ss
ss ss ds ss
Rhabdovirus Retrovirus
Paramyxovirus
Togavirus Picornavirus Reovirus Bunyavirus
Flavivirus Hepevirus Arenavirus
Calcivirus Orthomyxovirus
Coronavirus
Flavovirus
Deltavirus
Important notes about RNA viruses
- Retrovirus is the only RNA virus with complex capsid symmetry
- RNA structure is always ss except for Reovirus which is ds
- All RNA viruses have a linear RNA except for Bunyavirus and Arenavirus (circular)
- All RNA viruses have a non-segmented RNA except for Bunyavirus, Arenavirus,
Orthomyxovirus (segmented)
 RNA Viruses
Enveloped RNA Viruses Naked RNA Viruses
Steps in Virus Replication
Critical Steps in Virus Replication
Step 1: Adsorption/Attachment

• Virus adsorbs to cell surface via ionic interactions

• Virus attachment protein recognizes specific receptors (proteins, carbohydrates or
glycolipid components) on cell surface
• Cells without appropriate receptors for a virus are not susceptible to that virus
Virus Target Cell Receptor on Host Cell

HIV Th cells, macrophages, microglia CD4 plus CCR5 or CXCR4

EBV B lymphocytes CD21 = CR2
Rabies Neurons Acetylcholine receptor
Rhinovirus Respiratory epithelial cells ICAM-1
SARS-CoV-2 Respiratory epithelial cells ACE-2
Parvovirus B19 RBCs P antigen
Critical Steps in Virus Replication
Step 2: Entry/Penetration
A) Fusion with plasma membrane
(enveloped viruses)
- Virus envelope contains proteins that
promote fusion with cell plasma
membrane
- Internal components of the virion are
immediately delivered to the
cytoplasm
- Virus envelope incorporated into
plasma membrane promotes fusion
between infected and non-infected
cells

B) Endocytosis (enveloped and

naked viruses)
- Virus can be taken up by several
endocytsosis mechanisms: clathrin-
mediated endocytosis,
micropinocytosis or caveolar
endocytosis

C) Direct Penetration (naked viruses)

- Naked capsid human viruses can enter
the cell by crossing plasma membrane
directly
Critical Steps in Virus Replication
Step 3: Uncoating
- Release of viral genome from its protective capsid to enable nucleic acid to be
transported within the cell to be replicated, transcribed, and assembled into new
progeny virions
Step 4: Genome Replication
- Nucleic acid replication produces new viral genomes for incorporation into progeny virions

In general:
- DNA viruses mainly replicate in nucleus
- RNA viruses mainly replicate in cytoplasm
- Exceptions include:
→ Poxvirus (DNA virus) replicates in cytoplasm
→ Retroviruses [ (+)RNA virus ] replicate in nucleus
→ Orthomyxoviruses [ (-)RNA virus ] replicate in nucleus and cytoplasm

- DNA viruses, generally, encode their own DNA-dependent DNA polymerase (DNA-dep-DNA pol)
to replicate their genomes, but few (parvovirus and papillomavirus) use cellular DNA pol for genome
replication

- All ss RNA viruses encode their own RNA-dependent RNA polymerase (RNA-dep-RNA-pol) to
replicate their genomes

- In case of ds RNA virus (Reovirus), the positive strand can not be used as mRNA since it is H-
bonded to the negative strand
VI. GENOMIC
Critical ACTIVATION
Steps in Virus Replication
Step 5: Gene Expression
- Segmented genome is transcribed into monocistronic mRNAs while non-segmented
genome tends to produce polycistronic mRNA
- mRNA is translated to a polypeptide, and proteolytically processed into mature
proteins
- To use the cell translational machinery, viral mRNAs have control signals
recognized by the cell (i.e. ribosome-binding site, splice signals, poly-A signals)
- “Early” proteins are produced in the cell but are not packaged into the virion (non-
structural)
- “Late” proteins are usually present in virions (structural, capsid proteins)
- (+) RNA genome can be translated into a protein and is infectious

- (-) RNA genome needs to be converted into (+) RNA strand by viral RNA-dep-RNA-
pol then translated into a protein
Replication and Expression of the Viral Genome
i- dsDNA
Replication and Expression of the Viral Genome
ii- dsDNA
(Poxvirus)
Replication and Expression of the Viral Genome
iii- partial dsDNA (Hepadnavirus/HBV)

Partially

(reverse transcriptase)

Fully

pgRNA
Replication and Expression of the Viral Genome
iv- ssDNA
(Parvovirus)
Replication and Expression of the Viral Genome
v- dsRNA
Replication and Expression of the Viral Genome
vi- ss(+)RNA
Replication and Expression of the Viral Genome
vii- ss(+)RNA (Retrovirus)

(reverse transcriptase)
Replication and Expression of the Viral Genome

viii- ss(-)RNA
Single-stranded
+RNA viruses

Partial double-stranded
DNA viruses
Critical Steps in Virus Replication
Step 6: Assembly and Maturation

- Viral particles are assembled by packaging the viral nucleic acid within the capsid proteins
(process is called encapsidation) to form the basic virion structure. This process can take place
in:
i- Nucleus (Herpes virus, Adenovirus, Papovavirus)
ii- Cytoplasm (Picornaviruses, Poxvirus, Reoviruses)
iii- Cell surface (Influenza virus, Retrovirus)

- There may be a maturation step that follows the initial assembly process involving structural
changes in the particle:
→ cleavage of capsid proteins to form mature products
→ condensation of nucleoproteins with the genome

- For some viruses, assembly and maturation are inseparable.

- For other viruses, maturation may occur after the virus has left the cell (i.e. HIV)
Critical Steps in Virus Replication
Step 7: Release
Naked viruses
- Can rupture cell membranes and virions get released (cytolysis)
- Few can form aggregates that travel by vesicles to plasma membranes
- Vesicles then fuse with the membranes releasing virus aggregates

Enveloped viruses
- Bud out through cell membranes acquiring the lipid envelope and virus envelope
proteins.
- Budding may or may not kill the cell (most of the time causes cell senescence)
- Viral matrix proteins mediate the physical interaction between the nucleocapsid and
the virus envelope proteins (in cell membranes) forcing the particle out