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Introduction to Basics
Dr.T.V.Rao MD
Dr.T.V.Rao MD
History Virology
Smallpox was endemic in China by 1000BC. In response, the practice of variolation was developed. Recognizing that survivors of smallpox outbreaks were protected from subsequent infection, variolation involved inhalation of the dried crusts from smallpox lesions like snuff, or in later modifications, inoculation of the pus from a lesion into a scratch on the forearm of a child.
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Introduction to Virology
A virus is an obligate intracellular parasite containing genetic material surrounded by protein
Introduction to Virology
Recognizing the shape, size, and structure of different viruses is critical to the study of disease
Viruses have an inner core of nucleic acid surrounded by protein coat known as an envelope Most viruses range in sizes from 20 250 nanometers
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Viral Properties
Viruses are inert (nucleoprotein ) filterable Agents Viruses are obligate intracellular parasites Viruses cannot make energy or proteins independent of a host cell Viral genome are RNA or DNA but not both. Viruses have a naked capsid or envelope with attached proteins Viruses do not have the genetic capability to multiply by division. Viruses are non-living entities
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Koneman et al. Color Atlas and Textbook of Microbiology 5th Ed. 1997
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Virion
The complete infectious unit of virus particle Structurally mature, extracellular virus particles.
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Virion
envelope
Capsid
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Viral core
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Virion Structure
Lipid Envelope Nucleic Acid Protein Capsid Virion Associated Polymerase
Spike Projections
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Obligate intracellular parasites Extreme genetic simplicity Contain DNA or RNA Replication involves disassembly and reassembly Replicate by "one-step growth
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- geographic locations
Sendai virus, Coxsackie virus
- their discovers
Epstein-Barr virus
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ICOSAHEDRAL
helical nucleocapsid
ENVELOPED ICOSAHEDRAL
COMPLEX
nucleocapsid
HELICAL
ENVELOPED HELICAL
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Icosahedral
Adeno-associated Virus (AAV) Adenovirus B19 Coxsackievirus - A Coxsackievirus - B Cytomegalovirus (CMV) Eastern Equine Encephalitis Virus (EEEV) Echovirus Epstein-Barr Virus (EBV) Hepatitis A Virus (HAV) Hepatitis B Virus (HBV) Hepatitis C Virus (HCV) Hepatitis Delta Virus (HDV) Hepatitis E Virus (HEV) Dr.T.V.Rao MD
Herpes Simplex Virus 1 (HHV1) Herpes Simplex Virus 2 (HHV2) Human Immunodeficiency Virus (HIV) Human T-lymphotrophic Virus (HTLV) Norwalk Virus Papilloma Virus (HPV) Polio virus Rhinovirus Rubella Virus Saint Louis Encephalitis Virus Varicella-Zoster Virus (HHV3) Western Equine Encephalitis Virus (WEEV) Yellow Fever Virus
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Viral Structure
Varies in size, shape and symmetry VIP for classification 3 types of capsid symmetry:
Cubic Helical
Protein binds around DNA/RNA in a helical fashion eg. Coronavirus
(icosahedral)
Complex
Is neither cubic nor helical eg. poxvirus
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2. ssDNA viruses 3. dsRNA viruses 4. (+) sense ssRNA viruses (codes 5. (-) sense ssRNA viruses 6. RNA reverse transcribing viruses 7. DNA reverse transcribing viruses
where "ds" represents "double strand" and "ss" denotes "single strand".
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All viruses must produce mRNA, or (+) sense RNA A complementary strand of nucleic acid is () sense
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1) that we are classifying the virus itself, not the host 2) the nucleic acid genome
3) the shared physical properties of the infectious agent (e.g capsid symmetry, dimensions, lipid envelope)
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Envelope protein
Membrane protein Spike protein
Viral envelope**
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Icosahedral capsids
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ICOSAHEDRAL SYMMETRY
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ICOSAHEDRAL SYMMETRY
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ICOSAHEDRAL SYMMETRY
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ICOSAHEDRAL SYMMETRY
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Adenovirus
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Adenovirus
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Helical symmetry
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Helical
California Encephalitis Virus Coronavirus Hantavirus Influenza Virus (Flu Virus) Measles Virus ( Rubeola) Mumps Virus Para influenza Virus Rabies Virus Respiratory Syncytial Virus(RSV)
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Helical symmetry
How to assemble
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Helical symmetry
In 1955, Fraenkel, Conrat, and Williams demonstrated that tobacco mosaic virus (TMV) spontaneously formed when mixtures of purified coat protein and its genomic RNA were incubated together.
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Naked viruses( Non Enveloped ) Adeno-associated Virus (AAV) Adenovirus B19 Coxsackievirus - A Coxsackievirus - B Echovirus Hepatitis A Virus (HAV) Hepatitis E Virus (HEV) Norwalk Virus
COMPLEX SYMMETRY
surface view cross section
POXVIRUS FAMILY
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ENVELOPE
OBTAINED BY BUDDING THROUGH A CELLULAR MEMBRANE (except poxviruses) POSSIBILITY OF EXITING CELL WITHOUT KILLING IT CONTAINS AT LEAST ONE VIRALLY CODED PROTEIN
ATTACHMENT PROTEIN
RNA or DNA
Genome
The genome of a virus can be either DNA or RNA
DNA-double stranded (ds): linear or circular Single stranded (ss) : linear or circular RNA- ss:segmented or non-segmented ss:polarity+(sense) or polarity (nonsense) ds: linear (only reovirus family)
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DNA
RNA
double-stranded
single-stranded
doublestranded
single-stranded
line ar
circular
line ar
circular
linear
linear (circular)*
singl sing e le
multip le
singl e
multipl e
(+)sense
(-)sense
sing le
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multip le
sing le
multip le
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DNA VIRUSES
DOUBLE STRANDED SINGLE STRANDED NON-ENVELOPED COMPLEX ENVELOPED
ENVELOPED
NON-ENVELOPED
PARVOVIRIDAE
POXVIRIDAE
HERPESVIRIDAE HEPADNAVIRIDAE
CIRCULAR
LINEAR
PAPILLOMAVIRIDAE POLYOMAVIRIDAE
(formerly grouped together as the PAPOVAVIRIDAE)
ADENOVIRIDAE
Modified from Volk et al., Essentials of Medical Microbiology, 4th Ed. 1991 Dr.T.V.Rao MD 48
DNA viruses
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RNA VIRUSES
SINGLE STRANDED positive sense SINGLE STRANDED negative sense DOUBLE STRANDED
ENVELOPED
NONENVELOPED
ENVELOPED
NONENVELOPED
ICOSAHEDRAL
HELICAL
ICOSAHEDRAL
HELICAL
ICOSAHEDRAL
CORONAVIRIDAE
REOVIRIDAE
Modified from Volk et al., Essentials of Medical Microbiology, 4th Ed. 1991 Dr.T.V.Rao MD 50
RNA viruses
RECEPTOR
VIRUS
ICAM-1
polio
CD4
acetylcholine EGF
HIV
rabies vaccinia
CR2/CD21
HVEM
Sialic acid
Virus Replication
1 Virus attachment
1 5
2 3 4 5 6
2
3
7 6 8
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and entry Uncoating of virion Migration of genome nucleic acid to nucleus Transcription Genome replication Translation of virus mRNAs Virion assembly Release of new virus particles
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ADSORPTION
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PENETRATION
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CALLED
VIROPEXIS / ENDOCYTOSIS / PINOCYTOSIS
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Replicative cycle
As obligate intracellular parasites, Virus must enter and replicate in living cells in order to reproduce themselves. This growth cycle involves specific attachment of virus, penetration and uncoating, nucleic acid transcription, protein synthesis, maturation and assembly of the virions and their subsequent release from the cell by budding or lysis
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UNCOATING
NEED TO MAKE GENOME AVAILABLE
ONCE UNCOATING OCCURS, ENTER ECLIPSE PHASE ECLIPSE PHASE LASTS UNTIL FIRST NEW VIRUS PARTICLE FORMED
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SYNTHESIS OF VIRAL NUCLEIC ACID AND PROTEIN MANY STRATEGIES NUCLEIC ACID MAY BE MADE IN NUCLEUS OR CYTOPLASM PROTEIN SYNTHESIS IS ALWAYS IN THE CYTOPLASM
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RELEASE
LYSIS BUDDING THROUGH PLASMA MEMBRANE NOT EVERY RELEASED VIRION IS INFECTIOUS
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Transmission of Viruses
Respiratory transmission Influenza A virus Faecal-oral transmission Enterovirus Blood-borne transmission Hepatitis B virus Sexual Transmission HIV Animal or insect vectors Rabies virus
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Viruses enter the body of the host in a variety of ways, for example...
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INHALED DROPLETS in sneezing of coughing for example the COMMON COLD or INFLUENZA VIRUSES.
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or by
...
drinking water or eating raw food, for example, HEPATITIS A and POLIOVIRUS.
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also...
vertical transmission from mother to baby for example HIV, HEPATITIS B and RUBELLA...
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also...
bites of vector arthropods such as mosquitoes for example YELLOW FEVER, RIFT VALLEY FEVER and DENGUE.
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get well after a period of sickness to be immune for the rest of their lives. Examples are MEASLES INFECTION, RUBELLADr.T.V.Rao MD or German measles, MUMPS and many others...
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A bacteriophage
A bacteriophage is any one of a number of viruses that infect bacteria. They do this by injecting genetic material, which they carry enclosed in an outer protein capsid. The genetic material can be ssRNA, dsRNA, ssDNA, or dsDNA ('ss-' or 'ds-' prefix denotes singlestrand or double-strand) along with either circular or linear arrangement.
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Structure of Bacteriophage
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Classification of Bacteriophages
The dsDNA tailed phages, or Caudovirales, account for 95% of all the phages reported in the scientific literature, and possibly make up the majority of phages on the planet. However, other phages occur abundantly in the biosphere, with different virions, genomes and lifestyles. Phages are classified by the International Committee on Taxonomy of Viruses (ICTV) according to morphology and nucleic acid.
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Sub-viral agents
Satellites
Contain nucleic acid Depend on co-infection with a helper virus May be encapsidated (satellite virus) Mostly in plants, can be human e.g. hepatitis delta virus If nucleic acid only = virusoid
Viroids
Unencapsidated, small circular ssRNA molecules that replicate autonomously Only in plants, e.g. potato spindle tuber viroid Depend on host cell polII for replication, no protein or mRNA
Prions
No nucleic acid Infectious protein e.g. BSE
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Bovine spongiform encepahltits (BSE) mad cow disease, scrapie in sheep kuru & Creutzfeld-Jakob Disease (CJD) in humans
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Viroids
Viroids are small (200-400nt), circular RNA molecules with a rodlike secondary structure which possess no capsid or envelope which are associated with certain plant diseases. Their replication strategy like that of viruses - they are obligate intracellular parasites.
Dependovirus /Virusoids Viroids are small (200-400nt), circular RNA molecules with a rod-like secondary structure which possess no capsid or envelope which are associated with certain plant diseases. Their replication strategy like that of viruses - they are obligate intracellular parasites.
(Prions)
Prions are rather ill-defined infectious agents believed to consist of a single type of protein molecule with no nucleic acid component. Confusion arises from the fact that the prion protein & the gene which encodes it are also found in normal 'uninfected' cells. These agents are associated with diseases such as Creutzfeldt-Jakob disease in humans, scrapie in sheep & bovine spongiform encephalopathy (BSE) in cattle.
Programme Created by Dr.T.V.Rao MD for Medical and Paramedical Students in the Developing World Email
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