VIRUSES:

GENERAL PROPERTIES
PATHOGENESIS OF VIRAL INFECTIONS
EFFECTS OF VIRUSES ON CELLS
LABORATORIES DIAGNOSIS OF VIRAL INFECTIONS

M. Inge Lusida
Dept. of Microbiology, Airlangga University School of
Medicine/ Dr. Soetomo Hospital
Institute of Tropical Disease, Airlangga University

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Three main properties of viruses:

 small size: the smallest known infective agents

(20 nm – 300 nm); bacteria: 1000 nm; erythrocytes:
7500 nm.
 genome: contain only one kind of nucleic acid
(DNA or RNA).
 metabolically inert: no metabolic activity outside
susceptible host cells; do not possess active
ribosomes/ protein-synthesizing apparatus, although
some viruses contain enzymes.
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VIRUS STRUCTURE:
Consist of nucleic acid/ genome, surrounded by a protein coat
 Virion: the intact virus particle
 Capsid: the protein coat
 Capsomeres: the protein structural units of capsid
 Nucleic acid genome: either DNA or RNA
 Envelope: some virus particles are surrounded by a lipoprotein
envelope; containing viral antigens

A: Enveloped virus with icosahedral symmetry. Not all icosahedral viruses have
envelopes. B: Virus with helical symmetry.
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MORFOLOGI

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Families of Animal Viruses That Contain Members Able to Infect Humans

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CULTIVATION OF VIRUSES

Viruses can only replicate within living cells.

For culture in vitro, 3 main systems are used:
1. Tissue culture: sel diambil dari jaringan manusia/ hewan
dibiakkan dalam media buatan dalam tabung. Sel-sel ini
hidup & mengadakan metabolisme, shg. dapat
menunjang replikasi virus.
2. Chick embryo: beberapa virus dapat ditumbuhkan pada
sel embryo ayam.
3. Laboratory animals: sebelum ada cara-2 lain, virus
diisolasi dan di-inokulasi pada hewan coba, seperti tikus,
kelinci, kera.

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EFFECTS OF VIRUSES ON CELLS

1. Death: the infection is lethal; causes a cytopathic effect

(CPE) which kills the cell; e.g. multinucleated giant cells/
syncitia, inclusion bodies.
2. Transformation: the cell is not killed, but is changed from
a normal cell to a malignant or cancerous cell.
3. Latent infection: virus remains within the cell in a
potentially active state, but produces no obvious effects
on the cell’s functions.
4. Haemadsorption: some viruses have haemaglutinin in
their outer coats adheres to erythrocytes
agglutination

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 CYTOPATHIC EFFECT (CPE)

Uninfected cells

A: Enterovirus—rapid rounding of cells

progressing to complete cell destruction.

D: Hemadsorption. Erythrocytes adhere to

those cells that are infected by a virus that
causes a hemagglutinin to be incorporated Inge Lusida, Viruses
into the plasma membrane.
Effect of Physical and Chemical Agents on Viruses

 Heat: most are inactivated at 56oC for 30 min. or

100oC for a few seconds.
 Cold: stable at low temperatures, can be stored at
-70oC for years.
 Drying: variable
 Ultraviolet: inactivates viruses.
 Chloroform, ether and other organic solvents:
enveloped viruses are inactivated; those without
envelopes are resistant.
 Oxidizing & reducing agents: viruses are inactivated
by formaldehyde, chlorine, iodine & hydrogen peroxide.
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 (Effect of Physical and Chemical Agents on Viruses)

 Phenols: most viruses are relatively resistant.

 Virus desinfectants: the best are hypochlorite solution &
glutaraldehyde.
corrosive
Sensitization & irritation to users

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VIRUS DISEASES

Most are mild & the viruses makes a complete recovery;

many are silent in the body without causing any
symptoms, which sometimes cause severe disease in an
unusually susceptible patient. Few viral diseases are
severe with high mortality.

Viruses enter the body through 4 main ways:

 Inhalation: via respiratory tract.
 Ingestion: via gastrointestinal tract.
 Inoculation: through skin abrasions, mucous
membranes (e.g. sexual); transfusion; injections;
transplants; via the bite of an arthropod.
 Congenital: i.e. from mother to fetus.
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VIRUS GROWTH CYCLE
7 STAGES:

1. Adsorption/ Attachment
 To specific receptors on the cell membrane. Specific
receptors ~ species, tissue, phisiologic condition of the
cells (37oC: optimum; 4oC: slow)
2. Entry/ Penetration
 Complex: by invagination of cell membrane round virus
particle.
 In syncitia-producing viruses: by fusion of virus envelope
with cell membrane.

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3. Uncoating:
 Enveloped viruses: by fusion of virus envelope with cell
membrane.
 Cell enzymes strip off the virus protein coat.
4. Transcription
 production of virus mRNA
 carried out by host cell or virus enzymes.
5. Synthesis of virus components
a) Virus protein synthesis: structural (virus particle) & non-
structural proteins (mostly enzymes).
b) Virus nucleic acid synthesis: new virus genomes are
synthesized (by virus polymerase or replicase).
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 6. Assembly
a) New virus genomes & proteins are assembled to form
new virus particles.
b) May take place in the nucleus, cytoplasm or (with most
enveloped viruses) at the plasma membrane to form
virus envelope.
7. Release
by sudden rupture or by budding of enveloped viruses.

Virus genomes
o DNA or RNA
o Single or double stranded
o intact or segmented
o Linear or circular Inge Lusida, Viruses
 B: The growth cycle of a positive-sense,
single-stranded RNA virus.

A: The growth cycle of a nonenveloped, double-stranded DNA virus (1) After penetrating the host cell,
viral DNA is uncoated and enters the nucleus. (2) Viral genes are transcribed. (3) The mRNAs are
translated in the cytoplasm. Newly synthesized proteins enter the nucleus. (4) Viral DNA is replicated in
the nucleus, sometimes with the help of newly synthesized viral replication proteins. (5) Viral DNA and
viral structural proteins assemble in the nucleus to produce new progeny virions. (6) On rare occasions,
viral DNA may be incorporated into cellular Inge
DNALusida,
as a side effect of infection.
Viruses
(Reproduced with permission from Talaro KP: Foundations in Microbiology: Basic Principles, 6th ed. McGraw-Hill, 2008. © The McGraw-Hill Companies, Inc.)
Mechanisms of budding of enveloped viruses

(Reproduced with permission from Willey JM, Sherwood LM, Woolverton CJ: Prescott, Harley, and Klein’s Microbiology, 7th
ed. McGraw-Hill, 2008. © The McGraw-Hill Companies, Inc.)
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 PATHOGENESIS OF VIRAL DISEASES

Fundamental process of viral infection:

Expression of viral replicative cycle in a host cell
no apparent effect cytopathology with
accompanying cell death to hyperplasia or cancer

Steps in Viral Pathogenesis

A. Entry & Primary Replication.
 Route of entry: respiratory tract, mouth/ intestinal tract,
skin (mild trauma, injection, bites), urogenital, or
conjunctiva.
 usually replicate at the primary site of entry.
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B. Viral Spread & Cell tropism
 Many viruses produce disease at distant from their
point of entry, e.g. enteroviruses.
 Most common route of spread: via bloodstream or
lymphatics. Virus in the blood, called: viremia. The viremic
phase is short in many viral infections.
 Neuronal spread, e.g. in rabies, virus reaches the
brain; in herpes simplex, virus moves to ganglia to initiate
latent infections.
 Tend to exhibit organ & cell specificities; specific cell
surface receptors for that virus.

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 SPREAD OF
VIRUS
THROUGH
THE BODY

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Common Routes of Viral Infection in Humans

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C. Cell Injury & Clinical Illness
 Destruction of virus-infected cells in target tissues
 Physiologic alterations by the tissue injury

disease
Some tissues, e.g. intestinal epithelium, can rapidly
regenerate & withstand extensive damage. Differ from
e.g. brain

Clinical Illness:
General symptoms associated with many viral infections (:
malaise, anorexia), result from host response (: such as
cytokine production) or by direct killing the cells.
Clin. symptoms is an insensitive indicator.
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D. Virus Shedding
 Shedding usually occurs from the body surfaces involved
in viral entry.
 Occurs at different stages of disease, depending of
particular virus, at which time the host is infectious.

E. Outcome of Viral Infection

1. Recovery
 virus infections are usually self-limiting
 associated with viral clearance
 host factors influencing
2. Persistence: Chronic & Latent Virus Infections
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(2. Persistence: Chronic & Latent Virus Infections)
The virus persists for long periods of time in the host.
Chronic infections: virus can be continuously detected, often at
low levels, mild or no clinical symptoms. e.g. HBV, HCV
Latent infections:
 virus persists in an occult, or cryptic, form most of the time;
 there will be intermittent flare-ups of clinical disease;
 infectious virus can be recovered during flare-ups.
 e.g. HSV, HZV

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Inapparent or subclinical infections:
No overt sign of their presence.

Persistent viral infections may play a role in:

certain types of cancer.

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Inge Lusida, Viruses
• New viral diseases are emerging, termed “emerging
viral diseases,” as new agents are recognized,
known agents evolve and spread, and new host populations
become infected.

Ebola virus, avian influenza viruses, Nipah virus, hantavirus

pulmonary disease, human immunodeficiency
virus infection, dengue hemorrhagic fever, West Nile virus,
Rift Valley fever, and bovine spongiform encephalopathy
(the latter a prion disease).

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 Bioterrorism Agents
Some viruses are potential bioterrorism agents based on
ease of host-to-host transmission and mortality rates.

Ease of dissemination or transmission from person to person,

mortality rates, ability to cause public panic, and requirement for
public health preparedness.

smallpox and the viral hemorrhagic fevers;

highest risk bacteria include the agents of anthrax, botulism,
plague, and tularemia.

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REFERENCES:

1. Brooks GF, Carroll KC, Butel JS, Morse SA, and Mietzner
TA. Jawetz, Melnick, & Adelberg’s Medical Microbiology
26th ed. 2013. Lange Medical Books.
2. Brooks GF, Carroll KC, Butel JS, Morse SA, and Mietzner
TA. Jawetz, Melnick, & Adelberg’s Medical Microbiology
27th ed. 2016. Lange Medical Books.
3. Richman DD, Whitley RJ, Hayden FG. Clinical Virology.
4th ed. 2017. ASM Press, Washington, D.C.
4. Timbury MC. Notes on Medical Virology. 11th ed. 1997.
Churchill Livingstone.

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