Medical
Virology
Dept. of Medical Microbiology and Parasitology Shanghai Second Medical University
Shanghai, China.
General Virology
Conception Viruses
Virion
Size and Shape Structure Replication Viral Variation
Conception
Virology is the bioscience for study of
History
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,
Definition of Virus
Viruses may be
defined
as
acellular
organisms
whose
genomes
consist of
nucleic acid
, and which obligately
replicate inside host cells
using
host
metabolic machinery
and
ribosomes
to
form a
pool of components
which
assemble into particles called
VIRIONS
,
which serve to
protect the genome
and to
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.
Consequences of Viral Properties
Viruses are not living
Viruses must be infectious to endure in nature Viruses must be able to use host cell processes
to produce their components (viral messenger RNA, protein, and identical copies of the
genome)
Viruses must encode any required processes not
provided by the cell
Challenges the way we
define life
viruses do not respire,
nor do they display irritability 应应应 ; they do not move
they do not grow
they do most certainly reproduce, and may
Size and Shape
Methods
Size of Viruses
Methods of Analysis
Electron microscopy :
The resolution is 5nm (1nm = 10-9 m)
Size of Viruses
A small virus has a diameter of about 20nm.
Parvovirus
A large virus have a diameter of up to 400nm.
Shape of Viruses
Shapes of Viruses
:Brick-shaped
.
Virion
the complete infectious
unit of virus particle
Structurally mature,
Virion
Capsid
Viral core
Viral core
Viral core
The viral nucleic acid genome, In the
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 – (non-sense)
DNA RNA double-stranded single-stranded double-stranded single-stranded lin ear circular lin
ear circular linear linear (circular)
sin gle sin gle multi ple sin gle sin gle multi ple sin gle multi
ple (+)sense (-)sense
Viral Capsid
The protein shell, or coat, that
encloses the nucleic acid genome.
Functions: a. Protect the viral
nucleic acid. b. Participate in the
viral infection. c. Share the
Nucleocapsid
The core of a virus particle
consisting of the genome
plus a complex of proteins
. complex of proteins =
Structural
proteins +Non- Structural
Symmetry of
Nucleocapsid
Helical
Cubic
/Icosahedral
Helical symmetry
Helical
California Encephalitis Virus
Coronavirus
Hantavirus
Influenza Virus (Flu Virus)
Measles Virus ( Rubeola)
Mumps Virus
Parainfluenza Virus
Rabies Virus
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)
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)
Complex Virus Structures
A well known example is the tailed
bacteriophages such as T4.
The head of these viruses is cubic
Properties of naked
viruses
Stable in hostile environment
Not damaged by drying, acid, detergent, and heat Released by lysis of host cells
Can sustain in dry environment
Can infect the GI tract and survive the acid and
bile
Can spread easily via hands, dust, fomites, etc Can stay dry and still retain infectivity
Neutralizing mucosal and systemic antibodies are
Naked viruses( Non Enveloped )
Adeno-associated Virus
(AAV)
Adenovirus B19
Coxsackievirus - A Coxsackievirus - B Echovirus
Envelope
A lipid-containing membrane that
surrounds some viral particles.
It is acquired during viral maturation by a
budding process through a cellular membrane, Viruses-encoded
glycoproteins are exposed on the surface of the envelope.
Not all viruses have the envelope, and
Functions of envelope
Antigenicity
some viruses possess neuraminidase
Infectivity
Properties of enveloped
viruses
Labile in dry , arid environment
Damaged by drying, acid, detergent,
and heat
Pick up new cell membrane during
multiplication
Insert new virus-specific proteins
after assembly
Consequences of Properties for
enveloped viruses
Must stay moist
Must not infect the GI tract for survival Must be transmitted in the protective,
droplets, secretions, blood and body fluids
Must reinfect another host cell to sustain Humoral and cell-mediated immunity are
Enveloped
California Encephalitis Virus Coronavirus
Cytomegalovirus (CMV)
Eastern Equine Encephalitis
Virus (EEEV)
Epstein-Barr Virus (EBV) Hantavirus
Hepatitis B Virus (HBV) Hepatitis C Virus (HCV)
Hepatitis Delta Virus (HDV) Herpes Simplex Virus 1 (HHV1)
Rotavirus Rubella Virus
Saint Louis Encephalitis Virus
Smallpox Virus (Variola) Vaccinia Virus
Herpes Simplex Virus 2
(HHV2)
Human Immunodeficiency Virus (HIV)
Human T-lymphotrophic Virus (HTLV)
Influenza Virus (Flu Virus) Molluscum contagiosum Papilloma Virus (HPV) Polio virus
Rhinovirus
Varicella-Zoster Virus (HHV3)
Venezuelan Equine Encephal. Vir. (VEEV) Western Equine
Virion structure
Nucleocapsid(Naked Virus) = DNA
or RNA +Structural proteins
+Enzymes &Nucleic acid binding proteins
Enveloped Virus =Nucleocapsid+
Envelop
ed
Virus
Naked
Virus
CHEMICAL COMPOSITION
OF VIRUSES
Viral Protein
Viral Nucleic Acid
Viral Lipids
Viral Nucleic Acid
DNA-double stranded (ds): linear or circular
Single stranded (ss) : linear or circular
RNA- ss:segmented or non-segmented
Viral Protein
Structural protein
(Capsomere)
Enzyme
glycoproteins (spike/viral
System for the
propagation of viruses
People
Animals : cows;chickens; mice; rats;
suckling mice
Embryonated eggs
Organ and tissue culture
Organ culture
primary tissue culture cell lines: diploid
Cytopathic effect, CPE
CPE:Viral Cytopathological Effects
Cell death
Cell rounding/Degeneration/Aggregation Lass of attachments to substrate
Inclusion bodies in the nucleus or
cytoplasm, margination of chromatin
Syncytia: multinucleated giant cells caused by virus-induced cell-cell fusion
Cell surface changes
Viral antigen expression
Inclusions
TCD50,LD50,ID50
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, matureation and assembly of the virions and their
Initiation Phase
Attachment
Penetration
Attachment/Adsorption
Virus attaches to the cell surface.
Attachment is via ionic interactions which are temperature-independent.
Viral attachment protein recognizes
specific receptors on the cell surface
(These may be protein or carbohydrate or lipid components of the cell surface).
Cells without the appropriate receptors
PENETRATION
(Virus enters the cell)
Virions are either engulfed into
vacuoles by “endocytosis” or
the virus envelope fuses with
the plasma membrane to
facilitate entry
Enveloped viruses
Fusing
(A) Entry by fusing
with the plasma membrane. Some
enveloped viruses fuse directly with the
plasma membrane. Thus, the internal components of the
virion are immediately delivered to the
Endocytosis
(B)
Entry via endosomes at the cell
surface
Enveloped viruses
Some enveloped viruses require an acid pH
for fusion to occur and are unable to fuse directly with the plasma membrane. These viruses are taken up by invagination of
clathrin coated pits into endosomes. As the endosomes become acidified, the latent
fusion activity of the virus proteins
Non-enveloped viruses
Non-enveloped viruses may cross
the plasma membrane directly
may be taken up via
clathrin-coated pits into endosomes. They
then cross (or destroy) the
UNCOATING
Nucleic acid has to be sufficiently
uncoated that virus replication can begin at this stage. When the nucleic acid is
uncoated, infectious virus particles
cannot be recovered from the cell - this is the start of the ECLIPSE phase - which lasts until new infectious virions are made
Uncoating is usually achieved by cellular
BIOSYNTHESIS
genome synthesis
mRNA production
Flow of events during the
replication of Hepadna
Flow of events during the
Flow of events during
the replication of
Flow of events during
the replication of
Flow of events during the replication of orthomyxoviruses and
Maturation
The stage of viral replication at which a virus
ASSEMBLY
RELEASE
Disintegration : naked virus cause the host cell
lysis
Budding: enveloped viruses
Budding viruses do not necessarily
kill the cell. Thus, some budding
viruses may be able to set up
Products of viral
replication
Virion
DEFECTIVE VIRUS
ABORTIVE INFECTION
DEFECTIVE VIRUS
deficiency in some aspects of replication, but interfering the replication of normal viruses
ABORTIVE INFECTION
When a virus infects a cell (or host), but
cannot complete the full replication cycle ( not biosynthesize their components or not
INTERFERENCE
Interferon, IFN
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 –(non-sense)
The Structure & Complexity of Virus
Genomes
The nucleic acid comprising the genome may be
single-stranded or double-stranded, & in a linear, circular or segmented configuration.
Single-stranded virus genomes may be:
positive (+)sense, i.e. of the same polarity
(nucleotide sequence) as mRNA
negative (-)sense
The Structure & Complexity of
Virus Genomes
any virus genome will usually include the following:
Composition - DNA or RNA, single-stranded
or double-stranded, linear or circular.
Size & number of segments. Terminal structures.
Nucleotide sequence.
Coding capacity - open reading frames.
Regulatory signals - transcription enhancers,
Transfection
Infection of cells caused by nucleic
Variation
There are two important variation which relate well with medical practices
Antigenicity variation: In most viruse the
antigenicity is stable but in some viruses such as influenze virus the antigenicity may vary and cause the disease to
epidemic.
Virulence variation(Virulent viruses):
Mutation
Mutant
Variant
temperature
Interactions
when two genetically distinct viruses infect a cell
3 different phenomena can ensue
Recombination /Reassortment Complementation
Recombination
dsDNA viruses
Reassortment ( segmented
genomes)
Phenotypic mixing
The genome of virus A can be
CLASSIFICATION OF VIRUSES
---basis of classification
Virion morphology
Physicochemical properties of the virion
Virus genome properties
Virus protein proteries
Genome organization and replication
Antigenic properties
CLASSIFICATION OF VIRUSES
By 1995
--71 families, 11 subfamilies
--164 genera
For humans and animals
--24 families,
Survey of DNA-containing
Viruses
Parvoviruses:
human parvovirus B19
Papovaviruses:
papillomaviruses Adenoviruses:
47 types infecthumans
Herpesviruses:
human herpesvirus1-8
Survey of RNA-containing
Viruses
Picornaviruses Astroviruses Caliciviruses Reoviruses Arboviruses Togaviruses Flaviviruses Arenaviruses Coronaviruses: SARS
Retroviruses Bunyaviruses
Othomyxoviruses Paramyxoviruses: Rhabdoviruses:rabies
virus
Bornaviruses: BDV Filoviruses
DNA and RNA Viruses
应应应应应应 Headnasviridae 应
应应应应应应 Retroviridae
）
Viroids(
应应应
)
Viroids are small (200-400nt), circular
RNA molecules with a rod-like
secondary structure which possess no
capsid or envelope which are
Dependovirus /
Virusoids
应应应应
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
））
(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
