MEDICAL VIROLOGY

7 June 22
By: Awoke D
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Objectives
Upon completion of this part of the course, students will
be able to:

1. Define a virus and related terminologies.

2. Describe structure & properties of medically
important viruses
3. Illustrate classification of viruses
4. Explain virus infectious cycle
5. Illustrate Viral laboratory diagnostic techniques
6. Describe antiviral agents and their mechanism of
action
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Contents

▫ Introduction to viruses
▫ Structure of medically important virus
▫ Classification of medically important virus
▫ Virus infectious/replication cycle
▫ Virus host interaction
▫ Pathogenesis
▫ Diagnostic virology
▫ Epidemiology, Prevention and treatment: Antiviral
agents and vaccines
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Brainstorming
• What do you know about Small
viruses? pox
Their nature, properties,
unique characteristics….?

Monkey pox

Ebola
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Definition

• Viruses are submicroscopic the smallest obligate

intracellualr infectious agents that contain only one kind
of nucleic acid (RNA or DNA).

• Acellular organisms/particles which replicate inside host

cells using host metabolic machinery to form a pool of
components which assemble into particles called virions..
 Intro…
Virology

▫ Bioscience for study of viral nature and the relationship

between viruses and hosts.
▫ Subfield of medical microbiology.
▫ Study of virus and viral diseases

• Virology is the study of structure, metabolism, classification,

evolution of the mode of infection of viruses and of the use of
host genetic material and cell for reproduction.

• The knowledge of viruses is today helping many researchers to

find out the therapy for such deadly disease.
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Defn…

• A virus is minimally constructed of

two components:

1. A genome (RNA or DNA)

2. A protein coat (Capsid)
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Scope of Virology

• Evolution, Structure and Classification

• Ways to infect and exploit host cells for
reproduction
• Their interaction with host organism physiology
and immunity
• Disease they cause
• The technique to isolate and culture them
• Treatment, prevention and control
• Their use in research and therapy
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• Cells are capable of independent replication, can

synthesize their own energy and proteins, and can be
seen in the light microscope.

• In contrast, viruses are:

▫ Not cells;
▫ Not capable of independent replication, do not
respire, do not grow, do not move
▫ Can synthesize neither their own energy nor their
own proteins, and
▫ Too small to be seen in the light microscope (are
submicroscopic).
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• Viruses are inert in the extracellular environment;

▫ They replicate only in living cells, because they
cannot generate energy or synthesize proteins: they
are parasites at the genetic level

• The universe of viruses is rich in diversity;

▫ They vary greatly in structure, genome
organization and expression, and strategies of
replication and transmission.
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• The host range for a given virus may be broad or

extremely limited.

• Viruses are known to infect all higher animals,

plants and unicellular organisms such as
mycoplasmas, bacteria, and algae.
Bacteriophage!

• Medically important viruses?

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General characteristics of viruses

• Viruses are the smallest (20-300nm) infectious agents

• They are obligate intracellular
• Have characteristic infectious cycle
• Able to be transmitted: i.e. they are transmissible
• Able to redirect genetic and metabolism apparatus of
the host cell
• Genome: either DNA or RNA
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Characteristics …

• Have major features of Cellular organisms:

 Life cycle, defined stage of development,
 Organization, genetic variation

• Do not possess some features:

o No machinery of metabolisms and protein
synthesis: do not have a nucleus, cytoplasm,
mitochondria, or ribosomes.
o Can not reproduce outside the host cell: are
simply particles
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Characteristics …

• Viruses replicate in a manner different from that

of cells; i.e., do not undergo binary fission or
mitosis.

• One virus can replicate to produce hundreds

of progeny viruses, whereas one cell divides
to produce only two daughter cells.
: Summary 16
 STRUCTURE OF VIRUSES

oSize
oShape
oStructure
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Viruses have size and shape!

E. coli
100 nm
Poliovirus
Adenovirus

Influenzavirus Herpesvirus Variolavirus

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Shape of viruses
• Spherical
• Rod-shaped
• Brick-shaped
• Tadpole-shaped
• Bullet-shaped
• Filament
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Structural Components

• Mature virus particle

consists of either two
or three basic
components:
1. Genome
2. Capsid
3. Envelop: not all
viruses have this
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Components of the
complete virus particle
(virion)
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A Virus particle

lipid membrane (envelope)

Envelope proteins

Nucleic acid

Protein shell (Capsid)

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A VIRUS

CORE

HIV
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A. Genome
• The viral genome is either DNA or RNA, and viruses
are hence categorized as DNA or RNA viruses.

• The nucleic acid of DNA viruses is usually double-

stranded (ds) and linear or circular depending on
the family.

• The nucleic acid of RNA viruses is usually single-

stranded (ss), with the exception of the reoviruses,
and is also segmented in a number of virus families.
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Genome…
Viruses with ssRNA are divided into two groups:
1. Plus-strand : the RNA has the same polarity as the
viral mRNA and can thus function directly as mRNA.
 It is also called positive-strand or “sense” RNA
strand.

2. Minus-strand: the RNA has the polarity opposite to

that of the mRNA, and therefore cannot be translated
into proteins until it has first been transcribed into a
complementary strand,
▫ It is also called a negative-strand or “antisense” RNA
strand
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B. Capsid

• The capsid is the “shell” of virus-coded protein that

encloses the nucleic acid and is more or less closely
associated with it.

• The combination of these two components is often

termed the nucleocapsid.
• The capsid is made up of subunits, the capsomers.

• These are spherical or cylindrical structures composed

of several polypeptides.
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Capsid…

• The capsid protects the nucleic acid from

degradation.

• In all except enveloped viruses, it is responsible for

the attachment of the viruses to the host cell
(“adsorption,” and determines specific viral
antigenicity.

• Capsid of viral particle has different symmetry

based on the arrangement of capsid proteins .
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Viral Protein Shell symmetry

Cubic Helical Complex

(Herpes simplex virus) (Influenza virus) (Variola virus)

• All human viruses that have a helical nucleocapsid are

enclosed by an outer membrane envelope, i.e., there
are no naked helical viruses.
• Viruses that have an icosahedral nucleocapsid can be
either enveloped or naked
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C. Envelope
• The envelope which surrounds the capsid in several virus
families, is always dependent on cellular membranes.

• Both cell-coded and viral proteins are integrated in the

membrane when these elements are transformed into the
envelope, frequently in the form of “spikes” (or
peplomers).
• Enveloped viruses do not adsorb to the host cell with the
capsid, but rather with their envelope.

• The surface proteins of the virus are the principal antigens:

determinants of type specificity (often called the
serotype).
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Envelop...

• In general, the presence of an envelope confers instability

on the virus.

• Enveloped viruses are more sensitive to heat, drying,

detergents, and lipid solvents such as alcohol and ether
than are nonenveloped (nucleocapsid) viruses, which are
composed only of nucleic acid and capsid proteins.

▫ An interesting clinical correlate of this observation is that

virtually all viruses that are transmitted by the fecal–oral route
(those that have to survive in the environment) do not have
an envelope.
▫ Eg: HAV, poliovirus, coxsackievirus, echovirus, Norwalk virus,
and rotavirus.
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Other Components of Viral Particles

• Various enzymes
▫ RNA-dependent RNA polymerases in antisense viruses
▫ DNA polymerases in smallpox viruses
▫ RNA-dependent DNA polymerase (“Reverse transcriptase”) in
retroviruses (eg. HIV) and hepatitis B viruses.

• Hemagglutinin
▫ Some viruses (above all myxoviruses
and paramyxoviruses) are capable of
agglutinating various different
human or animal RBCs.

• Neuraminase
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Structures compared
Properties of naked viruses

37
Properties of enveloped viruses

38
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Summary
• All viruses

▫ Are small obligate intracellular particles.

▫ Minimally composed of capsid and NA (DNA or RNA) +
lipid containing envelop.
▫ Attach to their host cell with a specific receptor binding
protein;
▫ Requires the assistance of a host cell to reproduce its
genomic information.
▫ Host range is determined by the presence of specific host
attachment sites and cellular factors.
Summary: Basic virus structure

40
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Thank you!
 CLASSIFICATION OF VIRUSES

oRationale
oBasis used for viral 13 June
classification By: Awoke D
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• The taxonomic/classification system used for

viruses is artificial.
i.e., it does not reflect virus evolution and is
based on morphological and biochemical
criteria.

The two major components of the virus used in

classification are:
1. The NA (DNA, RNA, ss, ds, +/- sense...)
2. The capsid (its size, symmetry & envelop).
Classification of medically important virus families44
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DNA VIRUSES

DOUBLE SINGLE STRANDED COMPLEX ds

STRANDED NON-ENVELOPED ENVELOPED

ENVELOPED NON-ENVELOPED PARVOVIRIDAE POXVIRIDAE

HERPESVIRIDAE
HEPADNAVIRIDAE
CIRCULAR LINEAR

PAPILLOMAVIRIDAE ADENOVIRIDAE
POLYOMAVIRIDAE

All families shown are

icosahedral except for
poxviruses
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RNA VIRUSES

SINGLE STRANDED + SINGLE STRANDED ds

positive sense negative sense
ENVELOPED NONENVELOPED ENVELOPED NONENVELOPED

ICOSAHEDRAL HELICAL ICOSAHEDRAL HELICAL ICOSAHEDRAL

CORONAVIRIDAE Orthomyxoviridae
Picornaviridae REOVIRIDAE
Togaviridae Paramyxoviridae
Caliciviridae
Flaviviridae Rhabdoviridae
Retroviridae Filoviridae
Bunyaviridae
Arenaviridae
Major families of Human Viruses and their Characteristics 47
 Medical important DNA viruses

Family Virus Transmission Diseases

Adenoviridae Adenovirus contact, ingestion Respiratory, GIT, Eye and GUT
infections
Herpes simplex Direct contact, Keratoconjunctivitis, Skin
type 1 droplets Infections, Encephalitis
Herpes simplex sexual contact , Genital Herpes, Neonatal
type 2 Direct contact Herpes
Varicella Zoster conjunctiva, Chickenpox (Varicella), Herpes
virus droplets zoster (Shingles)
Cytomegalovirus Blood transfusion, infectious mononucleosis-like
Herpesviridae contact, illness - Fever , Retinitis
congenital Pneumonitis, Hepatitis, colitis,
Encephalopathy
HHV 6 &7 Contact, aerosol Roseala infantum.
Epstein-Bar virus Infectious mononucleosis, Oral
Hairy Leukoplakia, Burkett’s
lymphoma
Kaposi’s sarcoma Kaposi’s sarcoma
associated herpes
virus
 Medical important DNA viruses

Family Virus Transmission Diseases

Small pox inhalation Small pox

Molescus direct and indirect Benign epidermal
Poxviridae contangisum
contact , sexual rout e tumor
Monkey pox Zoonoses Lymphadenopathy
and skin rash
Parvoviridiae Human parvovirus inhalation , blood Fifth disease, aplastic
B19 (B19V) transfusion anemia,
Papoviridiae Human papiloma sexual contact, Direct Wart and cervical
virus contact cancer

Hepadinaviridae Hepatatitis B virus Direct contact, blood Hepatitis B

transfusion, sexual
contact , parental route
 Medical important RNA viruses
Family Virus Transmissi Diseases
on
Influenza virus Aerosol FLU’ or True influenza
Orthomyxoviridae (type A, B and C)

Parainfluenza Aerosol Croup (laryngotraheobroncitis)

virus Bronchiolitis, Flu-like
tracheobronchitis
Paramyxoviridae Measles virus Aerosol Measles
Mumps virus Aerosol mumps
Respiratory Aerosol Bronchiolitis, pneumonia
Syncitial virus infants
Picornaviridae Poliovirus Fecal-oral Poliomyelitis
Human Fomit/aerosol common cold
rhinovirus
Coxsackievirues Fecal-oral, polio-like paralytic disease,
( A and B) contact , Aseptic meningitis,
aerosol Herpangia, diarrhea and
conjunctivitis
 Family Virus Transmission Diseases

Coronavirus Aerosols , Fecal- upper respiratory tract

oral , Mechanical infection , Enteric
Coronaviridiae infections in infants

SARS Virus Aerosols SARS

SARS-CoV2
Reoviridiae Rotavirus fecal – oral route diarrhoea in nursery

Norwalk virus fecal – oral route Diarrhea in Adults

HIV 1 / 2 sexual contact, AIDS

parental
Retroviridae
HTLV 1 and 2 Causes T cell leukaemia

`
Rhabdoviridae Rabies virus Bite of rabid dog Rabies
/ animal
Family Virus Transmission Diseases

Dengue virus vector born dengue fever

Yellow fever
Flaviviridae virus vector born yellow fever

West Nile virus vector born encephalitis

Sindbis virus vector born Subclinical encephalitis

encephalitis virus ( vector born Encephalitis

Togaviridiae western, eastern,

venzuiella )

Rubella virus Aerosols Germen measles

Baltimore classification
"Group" Family Human pathogens (disease)
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dsDNA
Poxviridae Variola (smallpox); Orf (pustular dermatitis); Molluscum contagiosum (pustular dermatitis)
Herpesviridae Herpes simplex 1,2 (oral, genital herpes); Varicella-zoster (chickenpox); Epstein-Barr (mononucleosis);
Cytomegalovirus (neonatal abnormalities); HHV6 (roseola); HHV8 (Kaposi's sarcoma)
Adenoviridae Adenovirus (respiratory infection, conjunctivitis)
Polyomaviridae Polyomavirus (benign kidney infection, respiratory disease, leukoencephalopathy)
Papillomaviridae Papillomavirus (warts, genital carcinoma)
ssDNA
Anellovirus Unknown
Parvoviradae B-19 (fifth disease, fetal death)
Retro
Hepadnaviridae
Retroviridae
Hepatitis B ("serum" hepatitis)
HIV (aids); HTLV (leukemia)
Major viral
Major pathogens
diseases
dsRNA
Reoviridae Rotavirus (infantile gastroenteritis)
and the disease
caused they cause
by human
viruses
ssRNA (-)
Rhabdoviridae Rabies virus (rabies)
Filoviridae Ebola virus (ebola)
Paramyxoviridae Parainfluenza virus (respiratory infection); Mumps virus (mumps);
Respiratory syncytial virus (respiratory infection); Measles virus (measles)
Orthomyxoviridae Influenza virus (influenza)
Bunyaviridae Hantaan virus (hemorrhagic fever with renal syndrome)
Arenaviridae Lassa fever virus (hemorrhagic fever)
Deltavirus Hepatitis D (fulminant acute hepatitis)
ssRNA (+)
Picornaviridae Poliovirus (polio), rhinovirus (URI), Hepatitis A ("infectious" hepatitis)
Calciviridae Norwalk (gastroenteritis)
Hepevirus Hepatitis E (acute hepatitis)
Astroviridae Astrovirus (gastroenteritis)
Coronaviridae Coronavirus (respiratory infection)
Flaviviridae Yellow fever virus (yellow fever); Hepatitis C (hepatitis)
Togaviridae Eastern Equine encephalitis virus (encephalitis); Rubella virus (rubella)
 REPLICATION OF VIRUSES

• Over view
• Viral replication cycle
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Over view
Viruses multiply only in living cells.
• The host cell must provide the energy and synthetic
machinery and the low-molecular-weight precursors for
the synthesis of viral proteins and nucleic acids.

• The viral nucleic acid carries the genetic specificity to code

for all the virus-specific macromolecules in a highly
organized fashion.

• In order for a virus to replicate, viral proteins must be

synthesized by the host cell protein-synthesizing machinery.
▫ Therefore, the virus genome must be able to produce a usable
mRNA.
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Viral replication cycle

General steps in viral
replication cycle are following:
1. Adsorption
2. Penetration
3. Uncoating
4. Proliferation/Synthesis
5. Assembly
6. Release
The basic features of the
infectious cycle are similar for all

Antiretroviral drugs may interfere

one or more of this steps.
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1. Adsorption
• Virus particles can only infect cells possessing surface
“receptors” specific to the particular virus species.

• When a virus encounters such a cell, it adsorbs to it either

with the capsid or, in enveloped viruses, by means of
envelope proteins.

• It is therefore the receptors on a cell that determine whether

it can be infected by a certain virus. Eg:
▫ HIV binds to the CD4 receptor on cells of the immune
system,
▫ Epstein-Barr virus recognizes the CD21 receptor on B
cells.
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Adsorption
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Receptor-mediated Attachment
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2. Penetration and Uncoating

• Viruses adsorbed to the cell surface receptors then

penetrate into the cell by means of pinocytosis (a
process also known as viropexis).

• In enveloped viruses, the envelope may also fuse with

the cell membrane, releasing the virus into the
cytoplasm.

▫ Adsorption of such an enveloped virus to two cells at the

same time may result in cell fusion.
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Penetration and Uncoating…

• The next step is uncoating which involves the

release of the nucleic acid from the capsid

• Uncoating is apparently activated by cellular

enzymes, possibly with a contribution from cell
membranes as well.

• Uncoating may require acidic pH in the

endosome.
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3. Expression of Viral Genomes and Synthesis of

Viral Components
• The essential theme in viral replication is that specific
mRNAs must be transcribed from the viral NA for
successful expression and duplication of genetic
information.

• Once this is accomplished, viruses use cell components

to translate the mRNA.

• Various classes of viruses use different pathways to

synthesize the mRNAs depending upon the structure of
the viral nucleic acid
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Synthesis…

• In a DNA virus infection, cellular polymerases

transcribe mRNA in the nucleus of the host cell from
one or both DNA strands.

• An exception to this procedure is the poxviruses,

which use their own enzymes to replicate in the
cytoplasm.

• In viruses with antisense-strand ssRNA and dsRNA

the transcription of the genomic RNA into mRNA is
carried out by the viral polymerases.
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Virus with a ssRNA genome of (+) polarity that replicates

via a DNA intermediate (eg. HIV)
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4. Assembly and Release

• Newly synthesized viral genomes and capsid

polypeptides assemble together to form progeny
viruses.

• In general, non enveloped viruses accumulate in

infected cells, and the cells eventually lyse and
release the virus particles.

• Enveloped viruses mature by a budding process.

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Release…

• Virus-specific envelope glycoproteins are inserted

into cellular membranes;

▫ viral nucleocapsids then bud through the

membrane at these modified sites and in so
doing acquire an envelope.

• Budding frequently occurs at the plasma

membrane but may involve other membranes in
the cell.
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Release of enveloped virus from a host cell by the process of

budding
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• Enveloped viruses are not infectious until they

have acquired their envelopes.

• Therefore, infectious progeny virions typically

do not accumulate within the infected cell.

• Video1
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Summary

•Viral capsid/envelop surface mediate attachment to host

cell receptors. This interaction determines the host
specificity and organ specificity of the virus.
•The surface proteins are the targets of antibody.
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Thank you!
• Viral transmission
• Pathogenesis
• Diagnostic virology
• Vaccines and antiviral agents

14 June 22
By: Awoke D
Viral Transmission:

– Horizontal transmission
(direct or indirect)
– Vertical transmission

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Viral pathogenesis

• Viral pathogenesis refers to the interaction of viral

and host factors that leads to disease production.

• Pathogenesis is the process by which an infection

leads to disease.

• A virus is pathogenic for a particular host if it can

infect and cause signs of disease in that host
(human, animal or plant).

77
Pathogenic mechanisms of viral disease include:

A. Implantation of virus at the portal of entry,

B. Local replication,
C. Spread to target organs (hematogenously,
lympogenously or by neurogenic routes)
D. Spread to sites of shedding of virus into the
environment.

The fundamental process of viral infection is the

viral replicative cycle.
78
Examples of
dissemination of
virus to secondary
sites in the body.

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Effects of viral infection on the host cell
The response of a host cell to infection by a virus
ranges from:

1. Little or no detectable effect

2. Alteration of the antigenic specificity of the cell
surface due to presence of virus glycoproteins
3. Latent infections that, in some cases, cause cell
transformation; or, ultimately, to
4. Cell death due to expression of viral genes that shut
off essential host cell functions

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Types of viral pathogenesis

at the cellular level
Laboratory methods for the Diagnosis of viral disease

Methods:
• Virus isolation: on cell cultures, rarely in experimental
animals or hen embryos.

• Direct virus detection: by electron microscopy to

identify viruses or virus components directly.

• Serodiagnostics: involving assay of antiviral

antibodies of the IgG or IgM classes in patient serum.
Eg; Serology of HIV, HBsAg…

• Molecular techniques: like PCR

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Uni-Gold HIV Rapid Test
 86

Prevention and control of viral disease

How to prevent viral disease?

Primary, secondary and tertiary prevention

Control of viral spread
• Vaccination
• Elimination of vectors
• Treatment
• Quarantine
• Change in life style
Smallpox

Many viral diseases have been

brought under control using
immunization, vector
control and improving
sanitation.
Flu in USA, 1957 87
Viral Vaccines

General Principles
• Immunity to viral infection is based on the development of an
immune response to specific antigens located on the surface
of virus particles or virus-infected cells.
• For enveloped viruses, the important antigens are the surface
glycoproteins.

• Vaccination evokes an antibody response and stimulates T

lymphocytes.
• Most effective viral vaccines protect >90% of recipients and
produce fairly durable immunity.
88
• Types of Viral vaccines now available for use
include
1. Attenuated live viruses (eg. Polio, mumps)
2. Killed viruses (eg. influenza, rabies)
3. Recombinant vaccines (e.g. Hepatitis B)

– Vaccines shall bee safe and effective (i.e to activate

both T and B cells)

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Antiviral Chemotherapy

91
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• There are far more antibacterial drugs than antiviral

agents.

• This is a consequence of the difficulty of designing a

drug that will selectively inhibit viral replication.

• Because viruses use many of the normal cellular

functions of the host in their growth, it is not easy to
develop a drug that specifically inhibits viral functions
and does not damage the host cell.
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Antiviral…

• Unlike most antibiotics, antiviral drugs do not destroy

their target pathogen; instead they inhibit their
development.

• Antiviral drugs are required for viruses for which;

▫ No vaccine –availability or not highly effective
(rhinoviruses-serotypes, constantly changing-
influenza / HIV)
▫ To reduce morbidity /mortality
▫ To help immunosuppressed patients
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Cont’d…

• In theory, all the steps in the virus life cycle ranging from
entry to release can be explored as molecular targets for
antiviral therapy.

• The vast majority of antiviral drugs developed since the

1980s are anti-HIV drugs.

• These anti-HIV drugs block diverse steps of the HIV life

cycle, including
▫ Entry,
▫ Reverse transcription,
▫ Viral protein processing, and
▫ Integration.
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By: Awoke D

Mechanism action of antiviral agents…

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Classes of Antiviral drugs

1. Nucleoside analogs
(Majority antiviral drugs)
2. Nucleotide analogs
3. Non-nucleoside Reverse
Transcriptase Inhibitors
(NNRTI)
4. Protease inhibitors
5. Other types-
miscellaneous
Eg. Acyclovir and Zidovudine E.g. Cidofovir
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Classification of ant-viral drugs based on their use

 101

Cont’d…

• The first types of somewhat effective anti-viral drugs were

nucleoside analogues, developed several decades ago,
which are able to interfere with viral genome replication.

• Eg: Acyclovir (against HSV) and AZT (against HIV).

• All of these analogues lack a 3' OH.

• Thus, if they get incorporated into a
growing nucleic acid strand, no further
elongation will be possible, because all
nucleic acid synthesis requires a 3' OH
site for adding the next nucleotide.
 102

Cont’d…
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By: Awoke D
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Virus family Disease Drug Mechanism of Action

Video
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Summary
• What are viruses?
• What makes them different from a cell?
• Structure;
▫ Nucleic acid (DNA/RNA) in a protein shell, +/- lipid envelope
▫ Structure impacts on biological properties

• Classification;
▫ The classification of viruses is based primarily on the nature of
the genome and whether the virus has an envelope.

• Replication;
▫ Only in living cells
▫ Generic scheme: Attachment…..release
▫ Varying strategies depending on NA
 107

Summary…
• Viral pathogenesis
▫ Transmission: horizontal vs vertical
▫ Viral disease: a result of viral infection cycle, cell
damage and immunopathology.
▫ Pattern of viral disease: generalized vs localized
▫ Viral disease: acute, persistent
▫ Cytopathic effect: a range of effects including
transformation.

• Methods of diagnostic virology?

• Prevention and control of viral disease

▫ Vaccine: how they works, types of viral vaccines?
▫ Antiviral agents
 108

Reading assignment

• HIV
• Hepatitis viruses (HAV-E)
• SARS-CoV-2
• Cancer causing viruses
 109

Thank you