Download 1. animal virus

Introduction: Medical Virology
Akram Astani
Department of Microbiology
University of Yazd
Basics of Virology
VIRUSES?
First document of a virus infection
Ruma
1.500 B.C.
History of Virology:
discovery of viruses
 1882 A. Mayer: transmission of tobacco mosaic disease by plant extract;
pathogen can not be isolated
 1892 D. Ivanofsky: agent of tobacco-mosaic disease is ‚non filtratable‘ and
can not be propagated in culture medium
 1898 M. Beijerinck: the pathogen can be propagated in live tissue
The pathogen is: ultrafiltratable
does not replicate outside of live tissue
ultravisible
‚Contagium vivum fluidum‘; later Virus (lat. poison)
History of virology:
some important milestones
 1898: Loeffler and Frosch; foot and mouth disease virus (1. animal virus)
 1901: W. Reed; yellow fever virus (first human virus)
 1911: first discovery of a tumor virus (Rous Sarcoma Virus)
 1915: discovery of bacteriophages (Twort; d‘Herelle)
 1935: Crystallization of TMV (Stanley)
 1949: propagation of Polio virus (Enders, Weller, Robbins)
 1970: discovery of reverse Transcriptase (Baltimore, Temin)
 1977: Last case of pox (Somalia)
 1983: discovery of HIV
Peyton Rous
Medical importance of viral diseases
Leading causes of death in 2008 (World Health Report):
World
Deaths in millions
Ischaemic heart disease
% of deaths
7.25
12.8%
cerebrovascular disease
6.15
10.8%
Lower respiratory infections
3.46
(Influenza) 6.1%
disease
3.28
5.8%
Diarrhoeal diseases
2.46
(Rotavirus) 4.3%
HIV/AIDS
1.78
(Africa: 20%) 3.1%
cancers
1.39
2.4%
Tuberculosis
1.34
2.4%
Diabetes mellitus
1.26
2.2%
Road traffic accidents
1.21
2.1%
Stroke and other
Chronic obstructive pulmonary
Trachea, bronchus, lung
Measles: 1.4% (2000)
Differences between viruses
and bacteria
con. bacteria
Obligat. Intracell.
rickettsia
chlamydia
viruses
-
+
DNA and RNA
DNA and RNA
Protein synthesis
+
+
+
-
Energy metabolism
+
+
-
-
cell division
cell division
+
+
Nucleic acid
Replication
+
DNA and RNA
+
DNA or RNA
cell division
Assembly
Sensitivity towards
antibiotics
+
CHLAMYDIA: Obligate intracellular bacterial parasite which depends on eucaryotic cell for energy.
-
Viral origin
Two theories of viral origin can be summarized as follows:
May be derived from DNA or RNA nucleic
acid components of host cells
may be degenerate forms of intracellular
parasites.
Defining properties of viruses
• Viruses are the smallest infectious diseases (ranging from 20-300
nm)
•They are obligatory intracellular parasites without own metabolism
(being parasites at the genetic level)
• Viruses are completely dependent on their host cells for machinery
of energy production and synthesis of macromolecules.
• Virus progeny is assembled from newly synthesized components
Components of a virion
envelope
(Lipids+Proteins)
capsid (Protein coat)
genome (DNA or RNA)
-The entire infectious unit is termed a virion
- Capsid: The protein shell, or coat, that encloses the nucleic acid
genome
- Envelope: A lipid-containing membrane that surrounds some virus
particles
- Function of the outer shell (capsid, envelope):
• envelopment and protection of the Genome
• attachment to the host cell
- Nucleocapsid: Pr-nucleic acid complex
(Spike)
- Capsomers: Morphologic units , represents clusters of
polypeptides
- Matrix: protein layers in some viruses
- Spikes: glycoproteins, coded by virus
- Defective virus: A virus particle that is functionally
deficient in some aspect of replication.
Types of Symmetry of Virus Particles
Cubic Symmetry
In animal viruses :icosahedral pattern
Helical Symmetry
Complex Structures
Classification of viruses
1) By genome
Type of nucleic acid , size of genome in kilobases
RNA viruses
single strand
double strand
2) Virion Physicochemical
Molecular mass, buoyant density
DNA viruses
single strand
double strand
3) Virion morphology
Size, shape, type of symmetry
4) Biological properties
Natural host range, mode of transmission
‚Frontiers‘ of Virology
Viroid
genome
hosts
circular RNA
plant
Example
Coconut
Cadang Cadang
Virosoids
ss RNA
plant, human
*Hepatitis D Virus
* Need a helper virus (HBV) to replicate
Prion
human, animal
BSE
DNA VIRUSES
All are ds (double stranded) except Parvoviridae
All replicate in the nucleus except Poxviridae
Icosahedral
Naked (nonenveloped)
1- Parvoviridae
2- Papillomaviridae
3- Polyomaviridae
4- Adenoviridae
Enveloped
Complex
Enveloped
1- Herpesviridae
1- poxviridae
2- Hepadnaviridae
• Single-stranded DNA (linear), nonenveloped
viruses, icosahedral
• Parvo: small, very simple viruses,
Replication actively in dividing cells
- Densovirus (insect)
- Parvovirus (RA-1)
- Erytrovirus (B19, replicate in immature erythroid
cells, fifth diseases, apelastic crisis, Fetal death)
- Depoendovirus (requires helper virus, sattelite viruses
or virosoid : AAV, Adenovirus Associated Virus)
Double-stranded DNA (circular), nonenveloped
viruses,icosahedral, slow growth cycle
Polyomaviridae
– Persistence in kidneys; nephropathy, mainly in kidney
transplant recipients (BK virus)
– PML (Progressive multifocal leucoencephalopathy) with (JC
virus) inflammation of the white matter of the brain
– SV40 (Simian vacuolating virus 40), tumor in animals,
association with human tumor???(maybe)
BKV inclusion
Double-stranded DNA (linear),
nonenveloped viruses, icosahedral
-Respiratory and gastroenteritis infections in
humans
- Tumors in animals especially Hamster
Papillomaviridae
Double-stranded DNA (circular), nonenveloped
viruses, icosahedral, slow growth cycle
– Widespread in humans and other animals
– They causes ‘warts’
– Persistent HPV infection is a necessary condition for the
development of cervical cancer
Double-stranded DNA (circular), enveloped viruses,
partly single -strand
use reverse transcriptase to produce DNA from mRNA
 Hepatitis B virus, causes acute and chronic hepatitis
 Inflammation of the liver and injury lead to cirrhosis
Complete Dane particle 42 nm, 28 nm electron dense core,
containing HBcAg and HBeAg. The coat and the 22 nm free
particles contain HBsAg
Double-stranded DNA (Linear), enveloped viruses,
Herpein (Greek)=to creep
Three subfamilies:
 Alphaherpesvirinae - HSV-1 and HSV-2 (oral and
genital lesions), VZV (chickenpox and shingles)
 Betaherpesvirinae - CMV, HHV-6, HHV-7 (T
lymphotropic)
 Gammaherpesvirinae - EBV (infectious
mononucleosis and association with human neoplasms),
HHV-8 (associated with Kaposi sarcoma)
Set up latent or persistent infection following primary
infection
HSV-1 Cold sore
Double-stranded DNA (linear), enveloped viruses,
complex
• Largest of all animal viruses
• Replicate in the cytoplasm
• Virus visible under the light microscope
All poxviruses tend to produce skin lesions
Involving humans
- Variola virus
•Variola major – high mortality- Small Pox
•Variola minor – low mortality- Alastrim
- Vaccinia Virus - artificial virus
(Current smallpox “vaccine”)
-Molluscum contagiosum
 Involving animals
• Cowpox
• Monkeypox
Reaction to Physical & Chemical
Agents
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
Heat & cold
Stabilization of Viruses by Salts
pH
Radiation
Ether Susceptibility
Detergents
Formaldehyde
Photodynamic Inactivation
Antibiotics & Other Antibacterial Agents
Common Methods of Inactivating Viruses for Various Purposes
Heat & Cold
• Heating: Icosahedral and non-enveloped viruses are more resistant than
helical and enveloped viruses
• Viral infectivity is generally destroyed by heating at 50–60°C for 30’ min
minutes, though there are some notable exceptions (eg, hepatitis B virus,
polyomaviruses).
• Viruses can be preserved by storage at subfreezing temperatures.
• Preserve at 4⁰C and less degrees
Stabilization of Viruses by Salts
• Viruses are preferentially stabilized by certain salts in concentrations of 1
mol/L.
• MgCl2, 1 mol/L, stabilizes picornaviruses and reoviruses;
• MgSO4 , 1 mol/L, stabilizes orthomyxoviruses and paramyxoviruses; and
Na2SO4, 1 mol/L, stabilizes herpesviruses.
• The stability of viruses is important in the preparation of vaccines, ie, Oral
Polio vaccine.
pH
• Viruses are usually stable between pH values of 5.0 and 9.0.
• Some viruses (eg, enteroviruses) are resistant to acidic
conditions.
• . All viruses are destroyed by alkaline conditions.
Ether Susceptibility
•
Ether susceptibility can be used to distinguish viruses
(Enveloped or nonenveloped viruses)
Detergents
• Anionic detergents, eg, sodium dodecyl sulfate (SDS), also solubilize viral
envelopes; in addition, they disrupt capsids into separated polypeptides.
• Cationic, not really application in virology
• Nonionic detergents:Triton X100, Nonidet P40, solubilize lipid constituents
of viral membranes, The viral proteins in the envelope are released
(undenatured).
Formaldehyde
• Formaldehyde destroys viral infectivity by reacting with
nucleic acid. (Combination with (A, G, C))
• Viruses with single-stranded genomes are inactivated much more readily
than those with double-stranded genomes.
• Formaldehyde has minimal adverse effects on the antigenicity of proteins
(production of inactivated viral vaccines).
Photodynamic Inactivation
• Viruses are penetrable to a varying degree by vital dyes such as toluidine
blue, neutral red, and proflavine
• Neutral red is commonly used to stain plaque assays so that plaques are
more readily seen.
Radiation
- Radiation: ionic (β, γ, X, …) and nonionic (UV
- inactivate infectivity of viruses
Antibiotics & Other Antibacterial Agents
• Antibacterial antibiotics and sulfonamides, ammonium
compounds, Organic iodine compounds have no effect on
viruses.
• Larger concentrations of chlorine are required to destroy
viruses than to kill bacteria
• Alcohols, such as isopropanol and ethanol, are relatively
ineffective against certain viruses, especially picornaviruses.
Common Methods of Inactivating Viruses for Various Purposes
• Sterilization : steam under pressure, dry heat, ethylene oxide,
and,,,.
• Surface disinfectants include sodium hypochlorite,
glutaraldehyde and formaldehyde
• Skin disinfectants include chlorhexidine and 70% ethanol