Virus Classification, Structure & Replication Youhua Xie(谢幼华) MOH&MOE Key Lab of Medical Molecular Virology Sh Shanghai h i Medical M di l College, C ll Fudan F d University U i it 复旦大学上海医学院 分子病毒学教育部/卫生部重点实验室 yhxie@fudan.edu.cn The Nature of Viruses Viruses are small infectious agents (diameter 20‐300 nm) Infectious agents smaller than viruses: viroids, prions Gi t virus: Giant i Mi i i Mimivirus (400 nm, genome size 1.2 Mb), Pandoravirus (1 um, genome size 1.9-2.5 Mb) The Nature of Viruses ¾ Viruses contain one kind of nucleic acid (DNA or RNA genome) inside a protein shell (capsid), which may be surrounded by a lipid bilayer y membrane ((envelope). p ) The resultingg complete p virus p particle is called a virion All Cellular Lives Survive in a Sea of Viruses ¾ ¾ Viruses are major players in the ecosystem, ecosystem infecting every cellular life z Animals: animal viruses z Plants: plant viruses z Archaea: archae viruses z Fungi: mycoviruses （真菌病毒） z Bacteria: bacteriophages (噬菌体） z …… Viruses constitute a substantial amount of biomass on the earth ( (eg. there th are 1030 bacteriophage b t i h particles ti l alone l iin waters t on th the earth) 1 phage weighs about 1 femtogram (10-15 gram ) 1030 phages weigh about = 10-15 x 1030 = 1015 gram = 1012 kilogram = 109 tons Viruses Are Obligate Cellular Parasites ¾ Viruses multiplicate (replicate) inside host cells ¾ Vi Viruses utilize tili cellular ll l machineries hi i for f replication li ti z synthesis of proteins z synthesis of membranes z synthesis of amino acid, carbohydrates and lipids z generatation of energy Selected Milestones in Virology Discovery Year Scientist Smallpox vaccine 1798 Edward Jenner Rabies vaccine 1885 Louis Pasteur 1892 1898 Dimitrii Ivanovski Martinus Beijerinck Rous Sarcoma virus 1911 Peyton Rous Bacteriophages and the plaque assay 1915 1917 Frederick Twort Felix d’Herelle Crystallization of tobacco mosaic virus 1935 Wendell Stanley and John Northrup 1946 Bacteriophage genes are DNA 1952 Alfred Hershey and Martha Chase 1969 Di Discovery off interferons i f 1957 Ali k Isaacs Alick I andd Jean J Li Lindenmann d Viruses are filtrable Tobacco mosaic virus Nobel prize i 1966 Selected Milestones in Virology Discovery Year Scientists Polio vaccines 1955 1960 Jonas Salk Albert Sabin Reverse transcriptase of retroviruses 1971 Howard Temin and David Baltimore 1975 Virus vectors and gentic engineering 1970s Paul Berg 1980 Cellular oncogene g in a retrovirus 1976 Michael Bishopp and Harold Varmus 1989 RNA splicing in adenovirus 1977 Phillip Sharp and Richard Roberts 1993 Discovery off Human Di H Immunodeficiency Virus 1983 B é Si Barré-Sinoussi i F. F & Montagnier M i L. L 2008 HBV vaccine (recombinant) 1986 HPV vaccine (recombinant) 2006 Nobel prize Virus Classification http://www.ictvonline.org/ “a virus species is a polythetic class of viruses that constitute a replicating lineage and occupy a particular ecological niche”. A “polythetic class” is one whose members have several properties i iin common, although lh h they h d do not necessarily il allll share a single common defining property. In other words, th members the b off a virus i species i are d defined fi d collectively ll ti l b by a consensus group of properties. Common Properties for Virus Classification ¾ Virion morphology ¾ Nature of genome in virion ¾ Presence or absence of lipid membrane (envelope) ¾ Genome organization and replication ¾ Antigenic properties ¾ Biological properties Current ICTV Virus Classification The most recent report: p "Virus Taxonomy: y IXth Report p of the International Committee on Taxonomy of Viruses", 2012 ¾ 目 Orders (-virale): 7 ¾ 科 Families (-viridae): 96 ¾ 亚科 Subfamilies (-virinae): 22 ¾ 属 Genera (-virus): 420 ¾ 种 Species: 2618 Current ICTV Virus Classification Order Nidovirale Family Coronaviridae Subfamily C Coronavirinae ii Genus Betacoronavirus Species Severe Acute Respiratory Syndrom Virus Nature Review Microbiology 2003 Baltimore Classification of Viruses II ssDNA I VI (+)ssRNA-RT ssDNA dsDNA VII dsDNA-RT IV III (+) ssRNA mRNA dsRNA (-) ssRNA (-) ssRNA V Vertebrate DNA Viruses Diagram of the vertebrate DNA viruses Prescott-Harley-Klein: Microbiology 5ed DNA Viruses That Are Pathogens of Human Diseases Virus Family Genome Virus Diseases Parvoviridae ss Parvovirus B19 fifth disease, aplastic crisis Polyomaviridae ds JC virus progressive multifocal leukoencephalopathy BK virus BK nephropathy in renal transplant patients Merkel cell virus Merkel cell skin carcinoma Papillomaviridae ds Some human papillomavirus cervical cancer, penile cancer and oral cancers ((eg. g Type yp 16, 18)) Adenoviridae ds Adenoviruses (>50 types) acute respiratory diseases, conjunctivitis, gastroenteritis (type 40 & 41) Poxviridae ds Smallpox virus (variola), Vaccinia virus, Molluscum contagiosum virus (MCV), etc. Skin lesions (smallpox, vaccinia, molluscum contagiosum) DNA Viruses That Are Pathogens of Human Diseases Virus Family Genome Virus Diseases Herpesviridae ds Herpes simplex virus 1 & 2 Oral and genital lesions Varicella-zoster Varicella zoster virus Chickenpox, shingles Epstein-Barr virus Infectious mononucleosis, associated with human neoplasms (Burkitt’ss lymphoma, (Burkitt Nasopharyngeal carcinoma) Cytomegalovirus can be life-threatening for the immunocompromised p Human herpesvirus type 6 & 7 Roseola infantuma (children) Kaposi sarcoma-associated virus Kaposi sarcoma sarcoma, primary effusion lymphoma, some types of multicentric Castleman's disease Hepatitis B virus acute and chronic hepatitis B, associated with hepatocellular carcinoma Hepadnaviridae ds-RT ds RT Vertebrate RNA Viruses Diagram of the vertebrate viruses Prescott-Harley-Klein: Microbiology 5ed RNA Viruses That Are Pathogens of Human Diseases Virus Family Genome Virus Diseases Picornaviridae + ss Polioviruses poliomyelitis Coxsackieviruses, Echoviruses & other enteroviruses Herpangina, Hand, foot and mouth disease, Neurological disease, Heart and muscle disease Rhinoviruses Common cold Hepatitis A virus Hepatitis A Astroviridae + ss Astroviruses Gastroenteritis C li i i id Caliciviridae + ss N Norovirus i G Gastroenteritis ii Togaviridae + ss Rubella virus Rubella Alphaviruses (Ross River, Eastern, Venezuelan and Western equine encephalitis viruses, chikungunya virus) fever, headache, maculopapular skin rash, arthralgia, myalgia and sometimes encephalitis RNA Viruses That Are Pathogens of Human Diseases Virus Family Genome Virus Diseases Flaviviridae + ss Yellow fever virus Yellow fever Dengue virus Dengue fever Japanese encephalitis virus Japanese encephalitis Hpetitis C virus Hepatitis C Human coronaviruses Common colds SARS-CoV Severe acute respiratory syndrome (SARS) Parainfluenza P i fl viruses i types I–IV P i fl Parainfluenza Measles virus Measles, acute measles encephalitis Mumps virus Mumps Respiratory syncytial virus Common cause of bronchiolitis in infants,, mayy be severe and potentially fatal in babies with underlying cardiac, respiratory or immunodeficiency disease Coronaviridae P Paramyxoviridae i id + ss - ss RNA Viruses That Are Pathogens of Human Diseases Virus Family Genome Virus Diseases Orthomyxoviridae - ss, seg. Influenza virus A, B IAV is generally responsible for pandemics and epidemics; IBV often causes smaller or localized and milder outbreaks Bunyaviridae - ss Hantaviruses Haemorrhagic fever with renal syndrome, y , HFRS Rhabdoviridae - ss Rabies virus Rabies Filoviridae - ss Marburg virus & Ebola virus Marburg virus disease and Ebola virus disease (severe, (severe haemorrhagic, febrile illnesses) Reoviridae ds, seg. Rotavirus the commonest cause of childhood diarrhoea Retroviridae + ss -RT HIV-1 AIDS HTLV-1 Adult T-cell leukaemia/lymphoma Tropical i l spastic i paraparesis i Human Viral Infections & Diseases Virus Structures ¾ Viruses display a wide diversity of shapes and sizes ¾ Viral capsid is made from proteins encoded by the viral genome (capsid porteins or core proteins) ¾ Viral capsid protein subunits (capsomeres) selfself assemble to form a capsid, in general requiring the presence of the virus g p genome ((together g called nucleocapsid) ¾ Viral capsid shape serves as the basis for morphological distinction Virus Structures ¾ Helical capsid z Composed of a single type of capsomer stacked around a central axis to form a helical structure, which may have a central cavity z This arrangement results in rod-shaped or filamentous virions Virus Structures ¾ Icosahedral capsid z The optimum way of forming a closed shell from identical sub-units z The minimum number of identical capsomers required is twelve, each composed of five identical sub-units Virus Structures ¾ Complex capsid z Neither purely helical nor purely icosahedral, and possess extra structures such as p protein that mayy p tails or a complex outer wall Poxvirus Viral Infection Cycle ¾ Invade a susceptible organism (host) ¾ Attach to and infect a permissive host cell ¾ Within the host cell, cell the viral genome directs the synthesis of the components, components by cellular machineries, needed for the replication of the viral genome ¾ New viral pparticles are formed by y de novo assembly y from newly-synthesized y y components within the host cell ¾ The progeny viral particles are transmitted to new host cells or new organisms ¾ The particles are disassembled inside the new cell, initiating the next infectious cycle Generalized Model of Viral Replication p Cycle y Replication p of dsDNA Virus Cellular RNA polymerase II mRNA dsDNA dsDNA Cellular or viral DNA polymerase proteins Replication p of ssDNA Virus mRNA proteins dsDNA ssDNA Cellular RNA polymerase II ssDNA cellular DNA polymerase Replication p of dsRNA Virus proteins (+) ssRNA dsRNA Viral RdRp dsRNA Viral RdRp Replication p of (+) ( ) ssRNA Virus proteins (+) ssRNA ((-)) ssRNA Vi l RdR Viral RdRp (+) ssRNA Vi l RdR Viral RdRp Replication p of (-) ( ) ssRNA Virus mRNA proteins (+) ssRNA ((-)) ssRNA Viral RdRp ((-)) ssRNA Viral RdRp Vi l RdR Viral RdRp Replication p of Retrovirus mRNA proteins dsDNA (+) ssRNA Cellular RNA polymerase II (+) ssRNA ((-)) ssDNA Viral reverse transcriptase Replication of dsDNA-RT Virus (Hepadnaviridae) Cellular RNA polymerase II Partial P ti l dsDNA dsDNA mRNA ((+)) ssRNA proteins ((-)) ssDNA Viral reverse transcriptase Partial P ti l dsDNA
