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Transcript
Evolutionary Microbiology
Chapter 4. Virus – Dust of Life
Jong-Soon Choi
Chungnam National Univ. GRAST
University of Science and Technology
Korea Basic Science Institute
63
2009 Swine Flu News



2009 flu (or swine flu) was an
influenza-A pandemic
Second pandemics involving
H1N1 (1st pandemic H1N1,
Spain flu 1918)
2009 New strain of H1N1,
triply re-assorted from bird,
swine and human flu
(Source: www.google.com)
64
20th Century Flu Pandemics
Most death records in human history
Cause
Time
Death #
Small pox
20th century
300~500M
Black death
1346~1353
75~200M
Spanish flu
1918~1919
50~100M
World War II
1937~1945
61M
AIDS
1997~
36M
World War I
1914~1918
10M
Pandemic
Year
Type
Approx.
People
Infected
Worldwide
Estimated
Deaths
Case
Fatality
Rate
Spanish Flu
1918~
1919
H1N1
500M (33%)
50-100M
2~3%
Asian Flu
1956~
1958
H2N2
?
1~4M
<0.2%
Hong Kong
Flu
1968~
1969
H3N2
?
1~4M
<0.2%
Seasonal
Flu
Every
Year
H3N2,
H1N1
340M-1B
(5-15%)
250~500K
/year
<0.1%
Swine Flu
2009~
2010
H1N1/09
10-200M
18,500
0.03%
(Source: www.google.com)
65
1918 Spain Flu
Spain flu 1918, Camp Funston in
Kansas
Spain flu was transmitted to Korea
(무오년 감기) via Siberia Train
 Korea, ~Jan 1919, 7.4M
Infected, 140K Died (2% fatality)
 Japan, ~1919, 160K Infected,
1.3K Japanese Died
Lonyearbien, Svalvard
1919 Tokyo
Japan
(Source: www.google.com)
66
1918 Spain Flu
Origin : Around Chicago (Mar 1918,
mild)  Freetown, Sierra Leone
(severe)  Worldwide
EM Picture of Spain Flu Virus
Influenza A : highly virulent
Influenza B : less virulent
Influenza C : non-virulent
Cytokine Storm
 1918 Spain flu targeted the
young and healthy, particularly
dead to 20~35 years olds
 Spread worldwide, hundreds of
M infected and 50~100M people
died (~5% world people)
(Source: www.google.com)
67
1918 Spain Flu
 RNA from a victim of
the 1918 pandemic
isolated from formalinfixed, paraffinembedded lung tissue
virulence
 Nine fragments of viral
RNA sequenced: a
novel H1N1 influenza
A virus belonging to
the subgroups that
infect humans and
swine, not the avian
subgroup
Phylogenetic tree of HA33 (A) and NA53 (B)
68
Historical Genocide
Christopher Columbus (1451~1506)
Supported by Espana Queen Isabel
Columbus Day : 2nd Monday of October
Amerigo Vespucci (1454~1512)
Italian Explorer, Supported
by Portugal, Died by malaria in
Sevilla, Brazil
Francisco Pizzaro
(1475~1541),
Spanish
Conquistador
Genocide of Aztec by Hernan Cotez (1485~1547)
Spanish Conquistador, First spreader of Smallpox
Conquered Inca
Empire
(Source: www.google.com)
69
Gun, Germs and Steel
Driving Forces
For Human History
Major Infectious Diseases in Humans
All evolved from Diseases of Animals:
- Smallpox
World Inequality
- Tuberculosis
by European
- Malaria
Conquest with
- Plaque
Guns, Germs and
- Measles
Steel
- Cholera
(Source: www.google.com)
70
WHAT is VIRUS?









VIRUS: a small infectious
agent that replicates only
inside the living cells of other
organism
VIRUS can infect all types of
life form : animals, plants to
microbes (bacteria, archaea)
Dmitri Ivanovsky discovered
Tobacco Mosaic Virus in 1892.
VIRUS is most abundant and
found in every ecosystem.
Virion : single infectious viral particle (DNA/RNA)
Viroids : plant infectious agent, only RNA
Virusoids : sub-viral particle
Bacteriophages : bacteria-infecting virus
Virophage : virus-infecting virus???
(Source: www.google.com)
71
VIRUS Diversity
0.5 Liter Sea Water  10M viral
species, 30B viral particles
Virus : the most abundant bioorganism
- In water: 104~108/mL, In soil:
108~109/gram
- Virus in biosphere: 1031 particles,
10-times number of all bacteria
- Total length of all virus when
lined-up: 200M Light Year
VIRUS can kill 20% bio-organisms
everyday in the ocean, keeping in
the healthy biosphere
(Source: www.google.com)
72
HOW Old is VIRUS?
 The Pharao Ramses V
died of smallpox in
1157 BC
 Smallpox reached
Europe in 710 AD and
transferred to America
by H. Cortez in 1520
 3.5M Aztecs died
during 1520~1522
 Rabies known
since around
2000 BC
An Egyptian stele thought
to depict a poliovirus
victim, 18th Dynasty
(1580~1350 BC)
 First written of
rabies in
Mesopotamian
Codex (1930BC)
A woodcut from the
Middle Ages showing a
rabid dog
(Source: www.google.com)
73
Origin of VIRUS
Viruses as Precursors of
Cellular Life??
 Rather than being derived from
existing cells or cellular genetic
elements, viruses may have
existed before cellular life.
 Self-replicating units in the
ancient virosphere may have
gained the ability to form
membranes and cell walls,
 Viruses then continued to evolve with
leading to evolution of the three
the evolving hosts.
domains of life.
VIRUS is independent cellular or
acellular?
(Source: www.google.com) 74
Origin of VIRUS
Regressive hypothesis
• Viruses may have once been small cells
• Over time, genes not required by their parasitism were lost.
• Bacteria (rickettsia, chlamydia) are living cells like viruses
can reproduce only inside host cells.
Cellular origin hypothesis
• Some viruses may have evolved from bits of DNA or RNA
that ‘escaped’ from the genes of a larger organism.
• The escaped DNA could have come from plasmids or
transposons (mobile genetic elements).
Viroid (Subviral agent), plant
pathogen, no protein encoded
Virophage ‘sputnik’ is
intermediate between virus and
viroid
Co-evolution hypothesis
• Called “virus-first hypothesis”, proposed that viruses may
have evolved from complex molecules of proteins and
nucleic acids.
(Source: www.google.com)75
Human VIRUSES
Frequently
Found Human
Viruses
• Enteric viruses
노로바이러스
• Chickenpox 수두
• Herpesvirus
헤르피스바이러스
• Wart 사마귀
(Source: www.google.com)
76
Deadliest VIRUSES on Earth
Ebola
Hantavirus
Ebola hemorrhagic
Rodent carried,
fever, discovered in
HFRS/HPS, found in
1976, 50~90%
Korean War, HPS,
mortality
38% mortality
LASSA
Marburg
West Africa rat
African green
carried, 15~20%
monkey as host,
mortality, antiviral
discovered in 1967,
drug developed
23~90% mortality
Dengue
Rabies
Mosquito carried, fever,
Mad dog carried,
severe headache,
2300BC, ~90%
mortality, CNS-zombie
hemorrhage, no vaccine,
~50% mortality
Smallpox
Influenza
The oldest virus, fever,
Most popular
skin rash, blistering,
airborne virus,
eradicated in 1979
~40% vaccines of
historically ~30% mortality
the strains
(Source: www.google.com)
77
Hantavirus – 1st isolated in Korea
 Bunyaviridiae family, single
stranded, negative-sense RNA,
enveloped
 Hantavirus hemorrhagic fever with
renal syndrome (HFRS), hanta
virus pulmonary syndrome (HPS) –
contaminated by rodent feces
 Hantavirus, first outbreak during
Korean War (1950~1953)
 Named for the Hantan River area
in South Korea, Hantavirus isolated
by Ho-Wang Lee in 1976
Hantavax
Hantavirus vaccine
Manufactured by 녹십자
(Source: www.google.com)
78
Viral Pathogenesis
Highly Lethal Ebola vs. Highly Contagious Flu
 EBOLA : 50~90 lethality
Spread only in
Central Africa
 FLU : less than 0.1% lethal
Highly contagious,
Wide spread worldwide
 WHO is smarter?
Viral Disease = Effects on the
host caused by the viral
replication and the host immune
responses
Natural Selection favors the development of low-virulence virus strains.
• Pathogen invades host first  Host has little or no Immune, high mortality
• Survivors against viral infection  Favorable for virus before dispersal to new
host
(Source: www.google.com)
79
80
Viral Pathogenesis
Replication of Virus
Attachment > Penetration > Uncoating >
Replication > Assembly > Release
Hemagglutinin
• Agglutinates RBCs in tissue culture
• Involved in viral attachment/ penetration
and membrane fusion
• 15 types
• Neutralizing Ab against HA is important for
host immunity
Neuraminidase
• Allows for penetration through NP mucous
layer to epithelial cells
• 9 types (Tami flu inhibit Nase)
• Facilitates release of virions by cleaving
sialic acid residues thus preventing
aggregation
80
(Source: www.google.com)
Human Monkeypox in Africa
 Monkeypox, similar to smallpox but
much less serious, virus can cause a
fatal disease in human.
 Monkeypox occurs primarily in
Central and West Africa.
 Monkeypox virus is transmitted to
people from a variety of wild animals
and it spreads in human population.
 No treatment or vaccine
available although smallpox
vaccination is 85% effective.
Smallpox
eradicated
in 1979
(WHO)
(Source: www.google.com)
81
MERS-CoV in South Korea
Middle-East Respiratory Syndrome
Coronavirus (MERS-CoV)
 Novel positive-sense singlestranded RNA virus of the genus
betacoronavirus
 Thought to spread from an
infected person’s respiratory
secretions; however, the precise
way not understood
• Outbreak occurred in South
Korea from May to July 2015
• Newly emerged beta-coronavirus
first identified in Saudi Arabia in
April 2012
• A total of 186 infected, 36 dead
(19.4% mortality)
(Source: www.google.com)
82
SARS in Southern China
Severe Acute Respiratory Syndrome
(SARS)
 A viral disease of zoonotic origin
originated by SARS-CoV
 Initially flu-like, later influenza-lie,
leading to pneumonia
• Outbreak occurred in Southern
China between 2002-Nov to
2003-Jul
• Eventual 8096 cases and 774
deaths with the majority of cases
in Hong Kong (9.6% fatality)
• SARS spread from HK to infect
individuals in 37 countries in
early 2003 and ended by 2004Jan
(Source: www.google.com)
83
Back to Swine Flu
How antigenic shift, or reassortment, can result in
novel and highly pathogenic
strains of human influenza
Swine strain
 Viral evolution is an important
aspect of the epidemiology of viral
diseases
such
as
influenza
(influenza virus), AIDS (HIV), and
hepatitis (e.g. HCV).
 Viral evolution contains point
mutations, genome rearrangement,
recombination and translocation.
Host inter-species re-assortment
makes difficult to treat epidemic
flu!!!
84
(Source: www.google.com)