Virus Classification, Structure & Replication · Coxsackieviruses, Herpangina, Hand, foot and mouth...
Transcript of Virus Classification, Structure & Replication · Coxsackieviruses, Herpangina, Hand, foot and mouth...
Virus Classification, Structure & Replication
Youhua Xie(谢幼华)Youhua Xie(谢幼华)
MOH&MOE Key Lab of Medical Molecular VirologySh h i M di l C ll F d U i itShanghai Medical College, Fudan University
复旦大学上海医学院
分子病毒学教育部/卫生部重点实验室分子病毒学教育部/卫生部重点实验室
The Nature of Viruses
Viruses are small infectious agents (diameter 20‐300 nm)
Infectious agents smaller than viruses: viroids, prionsGi t i Mi i i (400Giant virus: Mimivirus (400 nm, genome size 1.2 Mb), Pandoravirus (1 um, genome size 1.9-2.5 Mb)
The Nature of Viruses
Viruses contain one kind of nucleic acid (DNA or RNA genome)Viruses contain one kind of nucleic acid (DNA or RNA genome) inside a protein shell (capsid), which may be surrounded by a lipid bilayer membrane (envelope). The resulting complete virus particle y ( p ) g p pis called a virion
All Cellular Lives Survive in a Sea of Viruses
Viruses are major players in the ecosystem infecting everyViruses are major players in the ecosystem, infecting every cellular life
Animals: animal virusesPlants: plant virusesArchaea: archae virusesFungi: mycoviruses (真菌病毒)
Bacteria: bacteriophages (噬菌体)
……Viruses constitute a substantial amount of biomass on the earth ( th 1030 b t i h ti l l i t th(eg. there are 1030 bacteriophage particles alone in waters on the earth)
1 phage weighs about 1 femtogram (10-15 gram )1 phage weighs about 1 femtogram (10 gram )1030 phages weigh about = 10-15 x 1030 = 1015 gram = 1012 kilogram = 109 tons
Viruses Are Obligate Cellular Parasites
Viruses multiplicate (replicate) inside host cellsVi tili ll l hi i f li tiViruses utilize cellular machineries for replication
synthesis of proteinssynthesis of membranessynthesis of amino acid, carbohydrates and lipidsgeneratation of energy
Selected Milestones in Virology
Discovery Year Scientist Nobel iprize
Smallpox vaccine 1798 Edward JennerRabies vaccine 1885 Louis PasteurRabies vaccine 1885 Louis PasteurViruses are filtrable
Tobacco mosaic virus 18921898
Dimitrii IvanovskiMartinus Beijerinck1898 Martinus Beijerinck
Rous Sarcoma virus 1911 Peyton Rous 1966Bacteriophages and the 1915 Frederick Twortplaque assay 1917 Felix d’HerelleCrystallization of tobacco mosaic virus
1935 Wendell Stanley and John Northrup 1946mosaic virusBacteriophage genes are DNA
1952 Alfred Hershey and Martha Chase 1969
Di f i f 1957 Ali k I d J Li dDiscovery of interferons 1957 Alick Isaacs and Jean Lindenmann
Selected Milestones in Virology
Discovery Year Scientists Nobel Discovery Year Scientists Nobel prize
Polio vaccines 19551960
Jonas SalkAlbert Sabin1960 Albert Sabin
Reverse transcriptase of retroviruses
1971 Howard Temin and David Baltimore 1975
Virus vectors and gentic engineering
1970s Paul Berg 1980
Cellular oncogene in a 1976 Michael Bishop and Harold Varmus 1989gretrovirus
p
RNA splicing in adenovirus 1977 Phillip Sharp and Richard Roberts 1993Di f H 1983 B é Si i F & M i L 2008Discovery of HumanImmunodeficiency Virus
1983 Barré-Sinoussi F. & Montagnier L. 2008
HBV vaccine (recombinant) 1986HPV vaccine (recombinant) 2006
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 i i l h h h d il llproperties in common, although they do not necessarily all
share a single common defining property. In other words, th b f i i d fi d ll ti l bthe members of a virus species are defined collectively by a consensus group of properties.
Common Properties for Virus Classification
Virion morphology
Nature of genome in virionNature of genome in virion
Presence or absence of lipid membrane (envelope)(envelope)
Genome organization and replication
Antigenic properties
Biological propertiesBiological properties
Current ICTV Virus Classification
The most recent report: "Virus Taxonomy: IXth Report of p y pthe International Committee on Taxonomy of Viruses", 2012
目 Orders (-virale): 7
科 Families (-viridae): 96科 Families (-viridae): 96
亚科 Subfamilies (-virinae): 22
属 Genera (-virus): 420
种 Species: 2618种 Species: 2618
Current ICTV Virus Classification
Order Nidovirale
Family Coronaviridae
Subfamily C i iSubfamily Coronavirinae
Genus Betacoronavirus
SpeciesSevere AcuteRespiratory
Nature Review Microbiology 2003
Species RespiratorySyndrom Virus
Baltimore Classification of Viruses
II
ssDNA
II
dsDNA dsDNA-RT(+)ssRNA-RT ssDNA
IVI VII
(+)IIIIV
dsRNA(+) ssRNA mRNA
(-) ssRNA
(-) ssRNA
V
Vertebrate DNA Viruses
Diagram of the vertebrate DNA virusesPrescott-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 (eg. Type 16, 18)
cervical cancer, penile cancer and oral cancers( g yp )
Adenoviridae ds Adenoviruses (>50 types) acute respiratory diseases, conjunctivitis, gastroenteritis (type 40 & 41)
Poxviridae ds Smallpox virus (variola), Vaccinia virus, Molluscum contagiosum virus (MCV),
Skin lesions (smallpox, vaccinia, molluscum contagiosum)
etc.
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 virus Chickenpox, shinglesVaricella zoster virus Chickenpox, shingles
Epstein-Barr virus Infectious mononucleosis, associated with human neoplasms (Burkitt’s lymphoma,(Burkitt s lymphoma,Nasopharyngeal carcinoma)
Cytomegalovirus can be life-threatening for the immunocompromisedp
Human herpesvirus type 6 & 7
Roseola infantuma (children)
Kaposi sarcoma-associated Kaposi sarcoma primary effusionKaposi sarcoma-associated virus
Kaposi sarcoma, primary effusion lymphoma, some types of multicentric Castleman's disease
Hepadnaviridae ds-RT Hepatitis B virus acute and chronic hepatitis B,Hepadnaviridae ds RT Hepatitis B virus acute and chronic hepatitis B, associated with hepatocellular carcinoma
Vertebrate RNA Viruses
Diagram of the vertebrate virusesPrescott-Harley-Klein: Microbiology 5ed
RNA Viruses That Are Pathogens of Human Diseases
Virus Family Genome Virus Diseases
Picornaviridae + ss Polioviruses poliomyelitis
Coxsackieviruses, Herpangina, Hand, foot and mouth Echoviruses & other enteroviruses
disease, Neurological disease, Heart and muscle disease
Rhinoviruses Common cold
Hepatitis A virus Hepatitis A
Astroviridae + ss Astroviruses Gastroenteritis
C li i i id N i G i iCaliciviridae + ss Norovirus Gastroenteritis
Togaviridae + ss Rubella virus Rubella
Alphaviruses (Ross River, fever, headache, maculopapular skinAlphaviruses (Ross River, Eastern, Venezuelan andWestern 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
Coronaviridae + ss Human coronaviruses Common coldsCoronaviridae + ss Human coronaviruses Common colds
SARS-CoV Severe acute respiratory syndrome(SARS)
P i id P i fl i P i flParamyxoviridae - ss Parainfluenza viruses typesI–IV
Parainfluenza
Measles virus Measles, acute measles encephalitis
Mumps virus Mumps
Respiratory syncytial virus Common cause of bronchiolitis in infants, may be severe and , ypotentially fatal in babies with underlying cardiac, respiratory or immunodeficiency disease
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 andcauses smaller or localized and milder outbreaks
Bunyaviridae - ss Hantaviruses Haemorrhagic fever with renal syndrome, HFRSy ,
Rhabdoviridae - ss Rabies virus Rabies
Filoviridae - ss Marburg virus &Ebola virus
Marburg virus disease andEbola virus disease (severeEbola virus Ebola virus disease (severe, haemorrhagic, febrile illnesses)
Reoviridae ds, seg. Rotavirus the commonest cause of childhood diarrhoeadiarrhoea
Retroviridae + ss -RT HIV-1 AIDS
HTLV-1 Adult T-cell leukaemia/lymphomai l i iTropical spastic paraparesis
Human Viral Infections & Diseases
Virus Structures
Viruses display a wide diversity of shapes and sizes
Viral capsid is made from proteins encoded by the viralViral capsid is made from proteins encoded by the viral genome (capsid porteins or core proteins)
Viral capsid protein subunits (capsomeres) selfViral capsid protein subunits (capsomeres) self-assemble to form a capsid, in general requiring the presence of the virus genome (together called p g ( gnucleocapsid)
Viral capsid shape serves as the basis forViral capsid shape serves as the basis for morphological distinction
Virus Structures
Helical capsidHelical capsid
Composed of a single type of capsomer stacked around a central axis to form a helical structure, which may have a central cavity
This arrangement results in rod-shaped or filamentous virions
Virus Structures
Icosahedral capsidIcosahedral capsid
The optimum way of forming a closed shell from identicala closed shell from identical sub-units
The minimum number of identical capsomers required is twelve, each composed of five identicalcomposed of five identical sub-units
Virus Structures
Complex capsid
Neither purely helical nor purely icosahedral, and that may possess extra structures such as protein y p ptails or a complex outer wall
Poxvirus
Viral Infection Cycle
Invade a susceptible organism (host)Invade a susceptible organism (host)
Attach to and infect a permissive host cell
Within the host cell the viral genome directs the synthesis of the componentsWithin the host cell, the viral genome directs the synthesis of the components, by cellular machineries, needed for the replication of the viral genome
New viral particles are formed by de novo assembly from newly-synthesized p y y y ycomponents within the host cell
The progeny viral particles are transmitted to new host cells or new organisms
The particles are disassembled inside the new cell, initiating the next infectious cycle
Generalized Model of Viral Replication Cyclep y
Replication of dsDNA Virusp
mRNA proteinsCellular
RNA polymerase II
dsDNA dsDNA
Cellular or viralCellular or viral DNA polymerase
Replication of ssDNA Virusp
mRNA proteins
CellularRNA polymerase II
ssDNA dsDNA
cellular
ssDNA
cellularDNA polymerase
Replication of dsRNA Virusp
proteins
(+)dsRNA (+) ssRNA
Viral RdRp
dsRNA
Viral RdRpViral RdRp Viral RdRp
Replication of (+) ssRNA Virusp ( )
proteins
(+) ( ) (+)(+)ssRNA
(-) ssRNA
Vi l RdR
(+)ssRNA
Vi l RdRViral RdRp Viral RdRp
Replication of (-) ssRNA Virusp ( )
mRNA proteinsViral RdRp
( ) (+)
Viral RdRp
( )(-)ssRNA
(+)ssRNA
Viral RdRp
(-)ssRNA
Vi l RdRViral RdRp Viral RdRp
Replication of Retrovirusp
mRNA proteins
( )
CellularRNA polymerase II
(+)(+) (-)ssDNA dsDNA
Viral
(+)ssRNA
(+)ssRNA
Viralreverse transcriptase
Replication of dsDNA-RT Virus (Hepadnaviridae)(Hepadnaviridae)
mRNA proteinsCellular
( )
RNA polymerase II
( )P ti l P ti ldsDNA (+) ssRNA
(-)ssDNA
PartialdsDNA
PartialdsDNA
Viralreverse transcriptase