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VIRUS

VIRUS = poison
Obligate Intracellular Organisms
No metabolic Systems of their own; highly dependent
on its host cell
Composed of genetic material enclosed in a protein
coat
GENOME
DNA or RNA but not both; can be single or double
stranded depending on the species

DNA Viruses: Usually double stranded, and linear or


circular
RNA Viruses: Usually single stranded and segmented
GENERAL STRUCTURE OF VIRUSES

Viruses are extremely diverse in size and in structure


The smallest virus is approximately 28 nm in size
(poliovirus), while the largest is 750 nm (mimivirus).
Viral classification is based on the physical and
chemical properties of viruses, their structure and
morphology
Viruses

Copyright 2004 Pearson Education, Inc., publishing as Benjamin Cummings Figure 13.1
VIRAL NUCLEIC ACID

The viral genome is composed of either DNA or RNA


It can be double stranded (ds) or single stranded (ss),
linear or circular

VIRAL CAPSID

The function of the capsid is to protect the viral nucleic


acid from detrimental chemical and physical conditions
(e.g. disinfection).
The capsid is composed of a number of subunits
named capsomeres
Nucleic Acid Core
Capsid
Envelope
VIRAL CAPSID
Capsomeres are fundamental for the virus, as they give
the shape of the capsid, but also provide the virus with
resistance to chemical and physical agents.
The assembly of the capsomeres results in 4 different
architectural styles icosahedral, enveloped, helical
symmetries; a more complex structure

Bacterial viruses (bacteriophages) show a complex


structure consisting of a capsid head, a tail and tail
fibres
STRUCTURAL PATTERNS OF CAPSOMERES

4 TYPES
Helical
Icosahedral
Enveloped
Complex
GENERAL STRUCTURE OF VIRUSES
Capsomere

Capsid

1. Virion (virus particle)


2. Capsid (protein coat)
composed of Capsomere
(protein subunit)
protect the nucleic acid
Virion for attachment & entry to
to a host cell
GENERAL STRUCTURE OF VIRUSES
Capsomere Nucleic Acid
Nucleocapsid
Capsid

1. Virion
2. Capsid
3. Capsomere
4. Nucleic acid: DNA or RNA
5. Nucleocapsid
Virion
HELICAL
shaped like hallow
protein cylinders, which
may be either rigid or
flexible.
Nucleic acid and protein
are closely associated
Ex. Tobacco Mosaic
Virus, Ebola Virus
ICOSAHEDRAL
Polyhedrons / geometric
shape with 20 triangular sides
Assemble in a cubic manner
These capsids appear
spherical when viewed at low
power in the electron
microscope.
Can be crystallized and
viewed using
radiocrystallography
Ex. Adenovirus
ENVELOPED
Viruses that are enclosed in a
lipid rich envelope
Encloses the nucleocapsid
Variable in shape but the
capsid may be icosahedral or
helical
It is acquired during viral
maturation by a budding
process through a cellular
membrane
Ex. Influenza Virus
COMPLEX VIRUS
Capsid symmetry but not purely
icosahedral or helical
They may possess tails and
other structures (e.g. many
bacteriophages) or have
complex, multilayered walls
surrounding the nucleic acid
(e.g. poxviruses)
VIRAL ENVELOPE

The viral capsid can be surrounded by a lipidic


envelope, which originates from the host cell
Enveloped viruses are generally considered to be the
most susceptible to chemical and physical conditions
and do not survive well on their own outside the host
cell (e.g. on surfaces)
GENERAL STRUCTURE OF VIRUSES

6. Envelope:
Outer membrane,
Phospholipid layer with
a. Glycoprotein:
Spikes for
attachment to host
b. Matrix protein:
Connect envelope to
the capsid
Virion
GENERAL STRUCTURE OF VIRUSES

7. Enveloped nucleocapsid:
With envelope
8. Naked nucleocapsid:
Without envelope

Virion
Viral receptors

Important for viral infectivity as they


recognize the host cell receptor site
conveying viral specificity
VIRUS HOST CELL INTERACTIONS

Viruses can be considered as true intracellular parasites that


grow within living cells and use their energy and synthetic
machinery to produce viral components

Viruses are usually very specific and rarely cross species


barriers, although there are some exceptions, such as rabies
and influenza that can cause diseases in both animals and
humans
VIRUS HOST CELL INTERACTIONS
Viruses can interact with the host cell in five different ways:
(1) multiplication of the virus and destruction of the host cell upon release of
the viral progeny,
(2) multiplication of the virus and release of the virions without the immediate
destruction of the host cell,

(3) survival of the virus in a latent stage without noticeable changes to the
infected cell,
(4) survival of the infected cell in a dramatically altered or transformed state

(5) incorporation of the viral nucleic acid in the host cell genome without
noticeable changes to the infected cell
MULTIPLICATION OF HUMAN VIRUSES

Attachment to the host cell


Penetration of the viral particle
Uncoating of the viral particle
Replication of viral nucleic acids and translation of the
genome (transcription)
Maturation or assembly of virions
Release of virions into the surrounding environment
ATTACHMENT
First Step
Attachment and Interaction of Surface Proteins and
Receptors of the host cell
Specific
Examples of Receptors of Some Medically Important Viruses
Influenza Sialic Acid
Parainfluenza Gangliosides
Rabies Acetylcholine Receptors
HIV CD4 Receptor
EBV C3d
HSV1 Fibroblast Growth Factor
Measles CD46 and SLAM (signalling lymphocytic activation molecule)
PENETRATION
Varied mechanisms for penetration
Through:
Fusion with the cell membrane - enveloped virus
Endocytosis - cytoplasmic vacuoles
Translocation naked virus
Injection of Viral Material
UNCOATING

Disassembly
Loss of the protein coat
Exposes the nucleic acid
To make it available for transcription to occur
Uncoating is activated by cellular enzymes.
For DNA viruses the genetic material is released into the nucleus
while for RNA viruses, it is released in the cyotplasm
Attachment, Penetration, and Uncoating

Copyright 2004 Pearson Education, Inc., publishing as Benjamin Cummings Figure 13.14
TRANSCRIPTION AND TRANSLATION
Replication and expression of genetic material
DNA Viruses usually replicate in the nucleus
RNA Viruses replicate in the cytoplasm

3 Mechanisms common to all viruses:


transcription mRNA
translation protein
replication viral genome
ASSEMBLY AND RELEASE
Viral Maturation / Morphogenesis
Assembly of produced viral capsid proteins and genomes
Assembled to new infectious virions
Release of the new infectious virions
Ways of Release
Lysis of the Infected Cell
Exocytosis of viral particles
Budding off
Copyright 2004 Pearson Education, Inc., publishing as Benjamin Cummings
CULTIVATION OF HUMAN VIRUSES

The study and identification of viruses depends on our ability to


propagate them

The cultivation of many viruses enabled a better understanding


of their replication properties, more rapid diagnosis and the
easier production of vaccine
CELL CULTURE
Cells to support the growth of human viruses are usually derived from humans
or other primates, or from rodents
Cell cultures may be divided into three types according to their history: (1)
primary, (2) secondary and (3) continuous cell culture.

Primary cell lines are derived directly from an intact tissue such as human
embryo kidney or monkey kidney.
Secondary cell cultures are derived from primary cultures
A limited number of subcultures can be performed with these cells,
generally up to a maximum of about 50 before the cells degenerate

Continuous cell lines are usually derived from malignant tissue and have the
capacity to multiply indefinitely in vitro (HeLa cells-cervical CA)
Examples of Primary Cell Culture include
Human Embryonic Kidney (HEK)
Rabbit kidney (RK)
Primary Monkey Kidney (PMK)
Rhesus Monkey Kidney (RMK)
Cynomolgus monkey kidney (CMK)
African Green Monkey Kidney (AGMK)
CELL CULTURE
Chick embryo fertile chicken eggs, 9-11 days old
- grow pathogenic viruses

Animal inoculation culture


- source of cell lines for culture
VIRUS CLINICAL IMPORTANCE

1. VARIOLA - smallpox virus

2. HERPESVIRUS (HSV1 & HSV2) - HSV1 infects oral membrane in children


- HSV2 cold sore, genital herpes

Varicella zoster virus - Chickenpox in children


3. HEPATITIS VIRUS
HBV - Chronic infectious hepatitis, liver CA
HAV - infectious hepatitis
HCV - Blood transfusion
HDV - (co-infection w/HBV)Severe hepatitis
VIRUS CLINICAL IMPORTANCE

4. PAPILLOMA VIRUS - Cervical CA

5. INFLUENZA VIRUS - Upper respiratory tract (Myxovirus)

6. PARAMYXOVIRUS MUMPS VIRUS - Parotid gland swelling


- MEASLES VIRUS - Common childhood fever

7. TOGAVIRUS RUBELLA - German measles (pregnancy)

8. HIV - CD4 T-lymphocyte


CONTROL OF VIRUSES
Antiviral chemotherapy
HIV - slow disease progression HAART
Herpesvirus varicella cidofovir
Hepatitis B ribavarin and peginterferon-alpha
Influenza oseltamivir (swine flu outbreak)
VACCINATION

Viral vaccines are prepared using different methods,


the most common being the use of live attenuated
viruses, inactivated viruses or the use of viral
components

The attenuated viruses will cause a strong immune


response without causing the disease
VIRICIDAL EFFECTS OF CHEMICAL AND
PHYSICAL AGENTS ON VIRUSES

Viruses are generally transmitted via surfaces and therefore the


use of viricidal disinfectants on hard surfaces and viricidal
antiseptics on skin is important.
Biocidal activity depends upon a number of factors, such as
concentration, contact time and formulation
Most viruses are susceptible to exposure to temperatures above
60 C for 30 minutes

Viruses survive well at low temperatures and they can be routinely


stored at 40 C to 70 C
THE END