virus classification, structure &...

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

[email protected]

Why Study Viruses

Viruses are everywhere and infect all living things

Viruses cause human diseases

Viral infection of agricultural plants and animals can have

enormous economic and societal impact

Many thousands of copies of viral DNA are within the human y p

genome

Viruses are valuable tools to study and manipulate biologyViruses are valuable tools to study and manipulate biology

All Cellular Lives Survive in a Sea of Viruses

Viruses infect all living things

Animals: animal viruses

Plants: plant virusesPlants: plant viruses

Archaea: archae viruses

Fungi: mycoviruses （真菌病毒）Fungi: mycoviruses （真菌病毒）

Bacteria: bacteriophages (噬菌体）

Viruses constitute a substantial amount of biomass on the earth

There are 1030 bacteriophage particles alone in the world’s water supply.p g p pp y

1 phage weighs about 1 femtogram (10-15 gram )1030 phages weigh about = 10-15 x 1030 = 1015 gram = 1012 kilogram = 109 tons

Extend out into space for 200 million light years if arranged head to tail

Why Study Viruses






genome


An Egyptian stele thought to represent a polio victim, 18th Dynasty (1403–1365 BC) ( )

Human Viral Infections & Diseases

Why Study Viruses






genome


B k t li (i f ti f t li i i )b Ni l R b t (1624 1685) Broken tulips (infection of tulip mosaic virus)by Nicolas Robert (1624-1685)

Why Study Viruses






genome


Landmarks 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

Landmarks 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

Recombinant HBV vaccine 1986Recombinant HPV vaccine 2006

What Are Viruses

Small(20 300nm)(20-300nm)

ObligatoryAcellular

Obligatory cellular

parasitic

Diameter(nm)

Length(nm)

Agents smaller than viruses:viroids, prions

20

18-26

100 430

Parvovirus

Rh bd i

( ) ( )

45 100

20

100-430Rhabdovirus 45-100

140-260Poxvirus 220-450

300

>400Mi i i >400Mimivirus

E.coli 1-3000

What Are Viruses

Small(20 300nm)(20-300nm)

ObligatoryAcellular

Obligatory cellular

parasitic

Viruses Are Acellular Particles

Herpes Virus

Rhabdovirus

p

Phage PoxvirusPhage Poxvirus

What Are Viruses

Small(20 300nm)(20-300nm)

ObligatoryAcellular

Obligatory cellular

parasitic

Viruses Are Obligatory Cellular Parasites

Viruses multiplicate (replicate) inside host cells

Vi tili ll l hi i f li tiViruses utilize cellular machineries for replication

synthesis of proteins

synthesis of membranes

synthesis of amino acid, carbohydrates and lipids

generatation of energy

Basic Components of Viral Particles

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 viral particle y ( p ) g p p

is called a virion

Structures of Viral Capsids

Viruses display a wide diversity of shapes and sizes

Viral capsid is made from proteins encoded by the viral genome (capsid porteins or core proteins)

Viral capsid protein s b nits (capsomeres) self assemble to form aViral capsid protein subunits (capsomeres) self-assemble to form a capsid, in general requiring the presence of the virus genome (together called nucleocapsid)

Viral capsid shape serves as the basis for morphological distinction

Helical Capsid

Composed of a single type of capsomer stacked around aComposed 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

Icosahedral Capsid

The optimum way of formingThe optimum way of forming a closed shell from identical subunits

The minimum number of identical capsomers required is twelve eachrequired is twelve, each composed of five identical subunits

Complex Capsid

Neither purely helical nor purely icosahedral, and may possess extra structures such as protein tails or a complex outer wallextra structures such as protein tails or a complex outer wall

Poxvirus

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 inA polythetic class is one whose members have several properties in common, although they do not necessarily all share a single common defining property. In other words, the members of a virus species are d fi d ll ti l b f tidefined collectively by a consensus group of properties.

Common Properties for Virus Classification

Virion morphology

Biochemical nature of genome

Presence or absence of lipid membrane (envelope)

Genome organization and replication strategyg p gy

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

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


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


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



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



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

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 Virusesp

mRNA proteinsCellular

RNA polymerase II*

dsDNA dsDNA

Cellular or viralCellular or viral DNA polymerase

Replication of ssDNA Virusesp

mRNA proteins

CellularRNA polymerase II

ssDNA dsDNA

cellular

ssDNA

cellularDNA polymerase

Replication of dsRNA Virusesp

proteins

(+)dsRNA (+) ssRNA

Viral RdRp

dsRNA

Viral RdRpViral RdRp Viral RdRp

Replication of Positive ssRNA Virusesp

proteins

(+) ( ) (+)(+)ssRNA

(-) ssRNA

Vi l RdR

(+)ssRNA

Vi l RdRViral RdRp Viral RdRp

Typical Positive ssRNA Viral Genome

G f Pi iGenome of Picornaviruses

Replication of Negative ssRNA Virusesp g

mRNA proteinsViral RdRp

( ) (+)

Viral RdRp

( )(-)ssRNA

(+)ssRNA

Viral RdRp

(-)ssRNA

Vi l RdR

antigenomicViral RdRp Viral RdRp

Genome of Influenzaviruses

Segment Protein1 PB22 PB1,

PB1 F2PB1-F23 PA4 HA4 HA5 NP6 NA6 NA7 M1

M2

Negative ssRNA, segmented 8 NS1NS2

Replication of Retrovirusesp

mRNA proteins

CellularRNA polymerase II

(+)dsDNA (+)ssRNAIntegration into

host chromosome(-)

ssDNA(+)

ssRNAdsDNA

host chromosome

Viralreverse transcriptase

Replication of dsDNA (rt) Virusesp ( )

mRNA proteinsCellular

( )

RNA polymerase II

( )P ti l P ti ldsDNA (+) ssRNA(-)

ssDNAPartialdsDNA

PartialdsDNA

Viralreverse transcriptase

virus classification, structure &...

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