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Lecture 17
Objectives
• Understand the taxonomic and Baltimore classifications of viruses
• Be familiar with the names of the major viral families and some common human viruses
• Describe the 7 types of virus replication in the Baltimore scheme
• D
Describe
ib th
the steps
t iin viral
i l replication
li ti iin animal
i l cellsll ((cff bacteriophage
b t i h replication)\
li ti )\
• Describe the two approaches used by enveloped viruses in infecting cells
• Describe how enveloped viruses acquire their envelope and leave infected cells
• Describe the 4 different effects animal viruses can have on infected cells
• Discuss influenza virus as an example of a lytic virus, Baltimore class V
• Describe the steps involved in the replication of influenza virus
• Understand the important of haemagglutinin and neuraminidase proteins of influenza viruses in
typing viral strains
• Understand the concepts of antigenic shift and antigenic drift in influenza viruses
• Understand the concern about influenza pandemics and current concerns about “bird flu”
• Discuss poliovirus as an example of a lytic virus, Baltimore class IV virus
• Di
Discuss h
herpes simplex
i l virus i as an examplel off a virus
i capable
bl off llatent
t t iinfections
f ti and
daB
Baltimore
lti
class 1 virus
• Give examples of oncogenic viruses
• Discuss hepatitis B virus as an example of a Baltimore class VII virus and an oncogenic virus
• Discuss retroviruses as an example of Baltimore class VI viruses
• Describe the replication of retroviruses (eg HIV)
• Understand the routes of transmission of HIV and the prevalence of AIDS globally
• Understand the routes of transmission of viral infections
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Taxonomic approach
1. Poxviridae – eg small pox virus
2. Herpesviridae – eg herpes simplex virus
3. Hepadnaviridae – eg Hepatitis B virus
4. Retroviridae – eg lentivirus – HIV 1
5. Paramyxoviridae – eg parainfluenza virus III, measles
virus, mumps virus
6. Coronaviridae – eg SARS virus
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7. Picornaviridae – eg poliovirus
poliovirus, rhinovirus
rhinovirus, hepatitis A
virus,
8. Togaviridae – eg rubella virus
9. Flaviviridae – eg yellow fever virus, Hepatitis C virus
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Molluscum
Contagiosum
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e.g. Measles Rabies virus Ebola virus Influenza Lassa virus Hanta virus Rotavirus
Mumps virus
Para-
influenza
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Fig. 14.8
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Lytic infections
Example
Influenza
• Orthomyxoviridae
• ssRNA (-) – Baltimore Class V
• Linear genome, RNA in 7 or 8 strands
• Helical nucleocapsid
• Enveloped virus
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Structure of influenza virus. The diagram illustrates the main structural features of the
virion. The surface of the particle contains three kinds of spike proteins: the
hemagglutinin (HA), neuraminidase (NA), and matrix (M2) protein embedded in a lipid
bilayer derived from the host cell and covers the matrix (M1) protein that surrounds the
viral core.. (From Fields Virology, 4th ed, Knipe & Howley, eds, Lippincott Williams
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& Wilkins, 2001, Fig. 47-2)
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Fields Virology, 4th ed, Knipe & Howley, eds, Lippincott Williams & Wilkins, 2001, Table 47-1
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Influenza A reservoir
The reservoir of influenza A viruses. The working hypothesis is that wild aquatic birds are the primordial reservoir of all influenza viruses
for avian and mammalian species. Transmission of influenza has been demonstrated between pigs and humans (solid lines). There is
extensive evidence for transmission between wild ducks and other species, and the five different host groups are based on phylogenetic
analysis of the nucleoproteins of a large number of different influenza viruses. (From Fields Virology, 4th ed, Knipe & Howley, eds,
Lippincott Williams & Wilkins, 2001, Fig. 47-3.)
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Pandemics
1918 Spanish flu Possible emergence from swine or an Pandemic with >20 million deaths
(1) (H1N1 avian host of a mutated H1N1 virus globally
viruses like
swine flu)
1957 Asian flu Possible mixed infection of an animal Pandemic, H1N1virus disappeared
(2) (H2N2) with human H1N1and avian H2N2 virus
strains in Asia
1968 Hong Kong High probability of mixed infection of Pandemic, H2N2 virus disappeared
(2) flu (H3N2) an animal with human H2N2 and avian
H3Nx virus strains in Asia
1977 Russian flu Source unknown but virus is almost Benign pandemic, primarily
(3) (H1N1) identical to human epidemic strains involving persons born after the
from 1950. Reappearance detected at 1950s. H1N1 virus has cocirculated
almost the same time in China and with H3N2 virus in humans since
Siberia 1977
Azerbaijan 0 0 0 0 0 0 8 5 0 0 0 0 8 5
Bangladesh 0 0 0 0 0 0 0 0 0 0 1 0 1 0
Cambodia 0 0 0 0 4 4 2 2 1 1 0 0 7 7
China 1 1 0 0 8 5 13 8 5 3 3 3 30 20
Djibouti 0 0 0 0 0 0 1 0 0 0 0 0 1 0
Egypt 0 0 0 0 0 0 18 10 25 9 7 3 50 22
Indonesia 0 0 0 0 20 13 55 45 42 37 18 15 135 110
Iraq 0 0 0 0 0 0 3 2 0 0 0 0 3 2
Lao People's
Democratic 0 0 0 0 0 0 0 0 2 2 0 0 2 2
Republic
Myanmar 0 0 0 0 0 0 0 0 1 0 0 0 1 0
Nigeria 0 0 0 0 0 0 0 0 1 1 0 0 1 1
Pakistan 0 0 0 0 0 0 0 0 3 1 0 0 3 1
Thailand 0 0 17 12 5 2 3 3 0 0 0 0 25 17
Turkey 0 0 0 0 0 0 12 4 0 0 0 0 12 4
Viet Nam 3 3 29 20 61 19 0 0 8 5 5 5 106 52
Total 4 4 46 32 98 43 115 79 88 59 34 26 385 243
http://www.who.int/csr/disease/avian_influenza/country/cases_table_2008_06_19/en/index.html
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Transmission of influenza
•Direct contact
•Aerosol
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Lytic infection
Poliovirus
• Picornaviridae
• ssRNA virus (+) – Baltimore
Class IV
• Simple icosahedral
nucleocapsid
• Very small virus
• Polio
• Almost eradicated from the
world by effective vaccination
program
• http://www.polioeradication.or
Transmission
• Common vehicle (water)
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Latent infections
Herpes simplex virus and varicella-zoster virus
• Herpesviridae
• dsDNA
d DNA virus
i – Baltimore
B lti Cl
Class I
• Icosahedral nucleocapsid
• Enveloped
• cold sores (herpes simplex virus) and chicken pox and shingles
(varicella-zoster virus)
• Virus remains latent in the neurones of the sensory ganglia from
which they emerge to cause infections of the skin
Transmission
• Direct contact (chicken pox scabs)
• aerosol
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Oncogenic viruses
• Cancer the result of the loss of the cell’s normal control
of its growth
• Growth & division of cells regulated by at least 2 types of
genes
– Proto-oncogenes – promote growth
– Tumour repressor genes – restrain growth
• Changes in either can lead to uncontrolled growth and
so cancer …
• Initiation event of cancer process can be the activation of
a proto-oncogene
t i t an oncogene or inactivation
into i ti ti off the
th
tumour repressor gene
• Not always possible to prove direct link with oncogenic
virus
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Hepadnavirus
• Hepatitis B
• Very small genome – 3.4 kb
• G
Genome partially
ti ll dds-DNA
DNA – 1 strand
t d iincomplete,
l t bboth
th h
have gaps
• Once inside host cell viral DNA polymerase (carried in the virion)
completes the replication
• Polymerase is a versatile protein – contains DNA polymerase as
well as reverse transcriptase and acts as a protein primer for
synthesis of one of the DNA strands
• Replication of the genome involves transcription by host RNA
polymerase – viral reverse transcriptase then copies this into a DNA
molecule
Transmission
• Direct contact – body fluids of infected person
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•Chronic HBV infection can lead to cirrhosis and then to liver cancer
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Retroviruses
• Retroviridae
• ssRNA (positive strand) – Baltimore Class
VI
• Enveloped viruses
• Replicate via DNA intermediate – reverse
transcriptase
• First viruses to be associated with cancer
• HIV
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Retrovirus
• Cartoon of a
retrovirus
• Genetic map of a
typical retroviral
genome
• Genetic map of Rous
sarcoma virus –
retrovirus
t i th
thatt causes
malignant tumours in
birds
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Replication of a retrovirus
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Transmission of HIV
• Sexual transmission.
• Transfusion of infected
blood and blood
products.
• Vertical transmission.
• Needle sharing among
injecting drug users.
• Occupational exposure.
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