Download Virology

樊晓晖教授讲授
Virology
Viruses： contain only
Introduction：
one kind of nucleic
acidviron
(DNA or RNA)，
一、concept of virus and
Obligate intracellular
二、relation with humanparasites
beings
Importance in medical microbiology
Virion：intact、
Characteristics of viral mature，infectious
diseases
viral particle
3、Persistent disease
1、high infectivity
2、few effective drugs
4、Contributory factor in cancer
How is virus found
？
 1886, Mayer found tobacco disease
 1892, Iwanowaski confirmed this disease
was caused by tobacco mosaic virus.
 1896, Beigerink named virus.
Fig. Leaf of tobacco and EM of tobacco mosaic virus.
SARS(2002)!!!
Consequences of viral
infections
 Suffering, followed by recovery
 Persistent disease
 Fatal disease
 Congenital disease
 Contributory factor in cancer
 Contributory factor in other diseases
Some are asymptomatic!
Viruses can be useful
Vaccine development
Gene therapy
Tools to investigate host cells
What are viruses?
“A PIECE OF BAD NEWS
WRAPPED UP IN A PROTEIN”
What are viruses?
 Nucleic acid genome:

DNA or RNA
 Protein coat

Protection, entry
 Lipid envelope in some viruses
 Small

(20-400nm)
 Obligate intracellular parasites
GROWTH ON
ARTIFICIAL
MEDIA
DIVISION BY
BINARY
FISSION
CONTAINS
BOTH RNA
AND DNA
CONTAINS
RIBOSOMES
CONTAINS
MURAMIC
ACID
SENSITIVE TO
ANTIBIOTICS
BACTERIA
+
+
+
+
+
+
MYCOPLASMA
+
+
+
+
-
+
RICKETTSIA
-
+
+
+
+
+
CHLAMYDIA
-
+
+
+
-
+
VIRUSES
-
-
-
(-)*
-
-
* The arenavirus family appears to ‘accidentally’ package ribosomes, but these appear to play no
role in protein synthesis.
Consequences
Heavily parasitic on host cell
No broad range antibiotics
Host range
 May be insect/animal, insect/plant
 Do not cross eukaryote / prokaryote
boundary
 May be wide or narrow
Factors affecting host range
Cell surface receptors
Factors affecting host range
o Cell surface receptors
Availability of replication machinery
Factors affecting host range
Cell surface receptors
Availability of replication machinery
Ability to get out of cell and spread
Factors affecting host range
Cell surface receptors
Availability of replication machinery
Ability to get out of cell and spread
Host anti-viral response
Viral structure – some
terminology
Virus particle = virion
Protein which coats the genome = capsid
Capsid usually symmetrical
Capsid + genome = nucleocapsid
May have an envelope
Characterization of virus
(1)DNA/RNA,without cellular
structure
(2)Reproduce within cells
(3)Reproductive fission----Replication
C23 Size and shape of viruses
Section 1
Size and shape
•size：
Range from 20nm
to nm
300nm，most
•measurement：
less than150nm
• shape：
bricks…….
most are spheres, some are rods, bullets,
第23章
病毒的基本性状
第二节 病毒的结构和化学组成
Section 2 Structure and
composition of viruses
第23章
第二节 第一节
病毒的结构和化学组成
病毒的大小与形态
病毒的基本性状
structure：
nucleic acid
virion
nucleocapsid
capsid
Non-envelope virion
 Some viruses have an envelope surrounding the
nucleocapsid
nucleic acid
capsid
envelope
Enveloped virion
第23章
病毒的基本性状
第二节
第一节
病毒的结构和化学组成
病毒的大小与形态
core
In the centre of virion
Is composed of DNA or RNA
 functions：genome of viruse，
provide information of
propagation，genetics and
variation for virus
第23章
第二节 第一节
病毒的结构和化学组成
病毒的大小与形态
病毒的基本性状
capsid

The protein shell, or coat, that
encloses the nucleic acid genome. be
composed of capsomeres.
composition：protein
a. Protect the viral
nucleic acid.
 functions
b. Participate in the



viral infection.
c. Share the
antigenicity
第23章
病毒的基本性状
第二节 病毒的结构和化学组成
第一节 病毒的大小与形态
Symmetry of Nucleocapsid
 According to the difference of number
and arrangement of capsomeres ：

①helical(Influenza Virus et al)

②Icosahedral( most of sphere virus)

③Complex(Poxvirus,Phage)。
第23章
病毒的基本性状
第二节 病毒的结构和化学组成
第一节 病毒的大小与形态
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.
 composition：lipid、protein and glucose.
第23章
病毒的基本性状
第二节第一节
病毒的结构和化学组成
病毒的大小与形态
Functions
 Antigenicity
some viruses possess neuraminidase
 Infectivity
Peplomere/spike associated with
attachment and penetration of viruses
Lipid protein cause fever.
 Resistance
Damaged by drying, acid, detergent, and heat
第23章
第二节 病毒的结构和化学组成
病毒的基本性状
CHEMICAL COMPOSITION
OF VIRUSES
(一)、 Viral Nucleic Acid
diversity
intron
Clone and exprssion
(二)、 Viral Protein
•capsid
•Matrix and envelope
Structural
•Viral enzyme (polymerase)
nonstructural •Inhibitory protein
第23章
第三节 病毒的培养与增殖
病毒的基本性状
Section 3 culture and propagation of viruses
一、 Culture of Viruses
Grow in animal
Viruses must
live in cells by
means of
multiplication
methods
Embryonated eggs
Organ and tissue culture
Primary tissue culture cell lines
Tissue culture include
Secondary tissue culture cell lines
Tumor or immortalized cell lines
第23章
病毒的基本性状
第三节 病毒的培养与增殖
二、 propagation
二、 病毒的增殖
of viruses
 Unlike other microorganisms, viruses lack
their
enzymes
that
require
for
propagation, they must grow in susceptible
and living cells.
 Mode of propagation——multiplication
 Virus must enter and replicate in living cells in
order to “reproduce” themselves.
 Replicative cycle of viruses.
第23章
第三节 病毒的培养与增殖
病毒的基本性状
二、 病毒的增殖
Replicative cycle of viruses
This “growth cycle” involves specific attachment of
virus, penetration and uncoating, nucleic acid
transcription, protein synthesis, matureation and
assembly of the virions and their subsequent release
from the cell by budding or lysis

Concept
Step：
Attachment and penetration
Uncoating
Biosythesis
Maturation assembly and release
1、 Attachment and penetration
：
第23章
病毒的基本性状
第三节 病毒的培养与增殖
二、 病毒的增殖
 Attachment: includes two phases


① Attachment is via ionic interactions which are
temperature-independent
②
Viral
attachment
protein
recongnizes specific receptors on the
cell surface
 Penetration



Endocytoses
Fussing
Nucleocapsid directly penetrate
第23章
病毒的基本性状
第三节 病毒的培养与增殖
二、 病毒的增殖
2、Uncoating
 Uncoating is usually achieved by cellular
proteases “opening up” the capsid
Happen before penetration:
phage
 During the penetration
 Happen after penetration

第23章
病毒的基本性状
第三节 病毒的培养与增殖
二、 病毒的增殖
can not detect virions
in this phase
3、 BIOSYNTHESIS
 ECLIPSE phase ：
Basic step
•Mode of
biosythesis
第23章
病毒的基本性状
第三节 病毒的培养与增殖
二、 病毒的增殖
Basic step of biosythesis
 Transcribe early mRNA
 Translate early protein such as
polymerase and inhibitory protein.
 Replicate viral progeny nucleic acid
 Transcribe late mRNA and translate
late protein (Structural protein）。
dsDNA
Progeny dsDNA
Early
mRNA
Late mRNA
Early Pr
(polymerase)
Late Pr
(Structural Pr)
Herpesviruses
Flow of events during the replication
of dsDNA virus
mRNA
ssDNA
ds+/-DNA
Intermediate
state
Viral Pr
New
complementory
DNA as template
Replicate ssDNA
Human Papovavirus
Flow of events during the replication of ssDNA virus
(+)ssRNA
Being
mRNA
Translate early protein
dsRNA
（-）ssRNA
intermediate
state
As template 1、Togavirus
（+）ssRNA (late mRNA)
progeny（+）
ssRNA
（non-segmented RNA）
2、Tumor virus
Late protein
（ Segmented RNA ）
Flow of events during the replication of (+)ssRNA virus
(-)ssRNA
Protein
(+)mRNA
（structural and
nonstructual）
Viral polymerase
ds(+/-)ssRNA
（intermediate
state）
Progeny
(-)ssRNA
1、Rhabdovirus
（ non-segmented RNA ）
2、 Influenza virus
（segmented RNA）
Flow of events during the replication of (-)ssRNA virus
Following host
cell division
(+)ssRNA
Retro-polymerase
(+/-)dsRNA:DNA
RNase H
hydrolyse
(+)RNA
HIV
HTLV-I
DNA
polymerase
(+/-)dsDNA
Integrate host
chromosome(
pro-virus)
mRNA
Progeny virus
Viral protein
DNA
HTLV-II
Flow of events during the replication of retro-RNA virus
Gene expression and genome replication
Viral
(+) mRNA
第23章
病毒的基本性状
第三节 病毒的培养与增殖
二、 病毒的增殖
Methods for biosynthesis

dsDNA viruses；ssDNA viruses；
(+)ssRNA；(-)ssRNA viruses
retro RNA viruses；dsRNA
viruses.
第23章
病毒的基本性状
第三节 病毒的培养与增殖
二、 病毒的增殖
4、assembly、maturation
and release
 Enveloped viruses ：
budding
 Non-enveloped
viruses：
eruption of
cells.
第23章
病毒的基本性状
第三节 病毒的培养与增殖
三、Effect caused by viruses
1、 viruses propagate and cause
cell lysing--Cytopathic effect：
Non-enveloped viruses
2、 viruses propagate, cells do not lyse ：
Enveloped viruses
3、viral genes integrate intoTwo viruses infect one
DNA
viruses
orinhibit
retro-viruses
cell, one
virus
chromosome of host cell：
•Happen
in the
same
strain
of the
viruses
replication of
4、Interference of viruses
：
•Happen
in
different
strain
another virus
of viruses
•Dead viruses interfere
lived viruses
第23章
病毒的基本性状
第三节 病毒的培养与增殖
三、 病毒增殖的细胞效应
Mechanism of interference
 Interferon indirectly inhibit
replication of viruses
 Compete or destroy receptors on
host
cells,
change
the
metabolism of host cells
 Block the mRNA translation of
second virus.
第23章
病毒的基本性状
第三节 病毒的培养与增殖
四abnormal viral propagation
 defective virus ： deficiency in some aspects of
replication, but interfering the replication of normal
viruses (腺病毒伴随病毒, 丁型肝炎病毒)
缺陷干扰颗粒(Defective interfering particles, DIP)
 顿挫感染(abortive infection)：When a virus infects a
cell (or host), but cannot complete the full replication cycle
( not biosynthesize their components or not assemble
virions.), i.e. a non-productive infection.
第23章
病毒的基本性状
Section 4
Physical and chemical
effect on viruses
灭活（inactivation）： lose infectivity；
maintain antigenic properties ,ability to absorb
RBC；
physical factors：heat , cold, radiation；
chemical factors：ether, detergents and
formaldehyde.
第23章
病毒的基本性状
Section 5 classification of
viruses
1、 Virus genome properties
DNA viruses
2、 Virion morphology
3、 Virus protein proteries
Retro viruses
4、 Physicochemical properties of the virion
RNA viruses
第23章
病毒的基本性状
第五节 病毒的分类

卫星 (satellites)病毒,Dependovirus /Virusoids卫星病毒
分两类
RNA (拟病毒virusoid), help virus provides capsid
RNA encodes capsid
 类病毒(viroid): 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.
 朊病毒（prion)，亦称蛋白侵染子。
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.
Summary
 Viruses are the smallest infectious agents and contain
nucleic acid (RNA or DNA )as their genomnome.
 They are not cells and are too small to be seen in the light
microscope.
 They are basic life forms composed of a protein coat that
surrounds genetic material, certain viruses are further
enclosed by an external lipid bilayer membrane that
surrounds the capsid and may contain glycoproteins.
 They are energy-less and float around until they come in
contact with an appropriate cell.
 Replication of the genetic material occurs when the virus
takes control of the host cell's synthetic machinery.
 Viruses contain all of the information, but usually do not
possess all enzymes needs for replication.
第23章
病毒的基本性状
思考题
 1 Describe the structure of virus
病 毒 的 结 构 .composition of those
structures and their functions 各
结构有何化学组成？有何功能?
 2 Describe the replicative cycle of
viruses病毒的复制周期包括哪些阶段？
 3 Definition: nucleocapsid 、
defective virus、interference
Review questions
1. What are the two types of symmertry of viral
capsid?
2. What are the functions of viral proteins?
3. What is the composition of the viral envelope,
and how is it formed?
4. Which proteins of virus induce protective
antibody?
5. What are the differences between viruses and
prions?