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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)