Virion

Morphology:

Spherical

Envelope:

Yes

Diameter (nm):

120–160

Length (nm):

 

Structural components:

Core, capsid, envelope

Buoyant density (g/mL):

1.23–1.24

Buoyant density method:

CsCl

Lipid composition:

Envelope lipids are derived from cytoplasma membrane of host cell

Additional information:

Surface projections made by the spike (S) protein; some strains contain a second layer of surface projections made of HE protein

Genome

Nucleic acid:

RNA

Strandedness:

 

Polarity:

 

Configuration:

 

Segment organization:

Segment no. 1 (kb):

29.0–31.4

One segment(s):

29–31.4 (kb) total (calculated)

G + C content (%):

37.6–41.8

mRNA transcripts:

7–10

Open reading frames:

7–10

Additional information:

The genome contains a leader at the 5′ end and a poly(A) tail; genes are arranged in the order 5′-replicase-(HE)-S-E-M-N-3′, with a variable number of other genes that are believed to be non-structural

Replication

Entry mechanism:

Receptor-mediated endocytosis

Site of transcription:

Cytoplasm

Transcriptase:

Virus-encoded RNA-dependent RNA polymerase

Site of genome replication:

Cytoplasm

Replicase:

Virus-encoded RNA-dependent RNA polymerase

Replication intermediate:

Negative-strand RNA intermediate

Site of virion assembly:

Cytoplasm, the intermediate compartment

Egress mechanism:

Budding through the pre-Golgi and Golgi to the basolateral (MHV) surface

Additional information:

Only the membrane (M) and envelope (E) proteins are required for the production of virus-like particles (VLPs)

History

Year of event

Event

References

1949

Murine hepatitis coronavirus (MHV) associated with encephalomyelitis in mice

Cheever et al (1949)

1967

HCoV-OC43 isolated from patients with common cold

McIntosh et al (1967)

1968

Electron microscopy reveals that BCoV has a second, short surface protein (HE)

Bridger et al (1978)

1975

ICTV approves Coronaviridae family with one genus, Coronavirus

Tyrrell et al (1975)

1981

Spike protein shown to be responsible for membrane fusion

Holmes et al (1981)

1982

Leader sequence at 5′ of mRNAs is from 5′ of genome (MHV)

Lai et al (1982)

1982

First coronavirus gene (N) sequenced (MHV)

Skinner and Siddell (1982)

1983

Leader-primed transcription model proposed (MHV); discontinuous transcription during positive strand synthesis

Lai et al (1983)

1984

M protein (MHV) is located in Golgi membranes

Tooze et al (1984)

1985

Near start of genes is a sequence similar to 3′ end of the leader RNA at 5′ end of the genome (MHV)

Budzilowicz et al (1985)

1985

Coronavirus defective RNAs discovered (MHV)

Makino et al (1985)

1985

Homologous recombination achieved with MHV

Lai et al (1985)

1991

Cell susceptibility to MHV conferred by a receptor of the carcinoembryonic antigen family

Dveksler et al (1991)

1996

ICTV recognises Coronaviridae as containing 2 genera: Coronavirus and Torovirus

Cavanagh et al (1997)

1996

ICTV recognises the order Nidovirales containing families Coronaviridae and Arteriviridae

Cavanagh et al (1997)

1996

M and E proteins sufficient for the formation of virus-like particles

Bos et al (1996); Vennema et al (1996)

1997

Insertion of gene for green fluorescent protein into genome of MHV by recombination

Fischer et al (1997)

2000

In-vitro construction of chimeric coronaviruses that cross the species barrier

Kuo et al (2000)

1999

Insertion of a transcription control sequence into MHV by recombination

Hsue and Masters (1999)

2002

A novel coronavirus (SARS-CoV) recognised as aetiological agent of severe acute respiratory disease (SARS) in humans in Guandong Province, China

Drosten et al (2003); Ksiazek et al (2003); Peiris et al (2003)

2003

Angiotensin-converting enzyme 2 recognised as functional receptor for SARS-CoV

Li et al (2003)

2003

SARS-like CoVs identified in wild carnivores sold at live markets in Guandong Province, China

Guan et al (2004); Tu et al (2004)

2005

Bats recognised as natural reservoirs of SARS-like CoVs

Lau et al (2005); Li et al (2005)

2005

Specific changes detected in the spike protein and accessory proteins 3a and 8 of SARS-CoV

Song et al (2005)

2005

Human coronavirus HKU1 identified in the nasopharyngeal aspirates of patients with pneumonia in Hong Kong

Woo et al (2005)

2005

Design of wide-spectrum inhibitors of coronavirus main protease

Yang et al (2005)

2005

Transcriptomics and proteomics approaches proposed for coronaviral infections

Jiang et al (2005)

2006

A common ancestor is recognised for BCoV, HCoV-OC43 and PHEV

Vijgen et al (2006)

2007

Identification of coronavirus interferon antagonist proteins

Ye et al (2007)

2009

ICTV recognises the family Coronaviridae as containing two subfamilies, Coronavirinae and Torovirinae, with the former including three genera

Carstens (2010)

2009

According to the new taxonomy, genus Coronavirus is replaced by genera Alpha-, Beta- and Gammacoronavirus, corresponding to the old antigenic groups

Carstens (2010)

2009

BCoV, HCoV-OC43, PHEV, CRCoV and related viruses are recognised as host variants of a unique species, Betacoronavirus-1, of the genus Betacoronavirus

Carstens (2010)

2009

SARS-CoV and bat SARS-CoVs are recognised as host variants of a unique species, SARSr-CoV, of the genus Betacoronavirus

Carstens (2010)

2010

An important role in the coronavirus lyfe cycle is assigned to the ubiquitin-proteasome system

Raaben et al (2010)

Genus Members

Species name

Synonyms

Wild-type strains/isolates

Natural host range

Experimental host range

Membership status

Murine coronavirus

Murine hepatitis virus (MHV); Rat coronavirus (Rat sialodacryoadenitis coronavirus) (RtCoV [SDAV]); Puffinosis coronavirus (PCoV)

MHV: A59, JHM; RtCoV: Parker, SDAV-681

Mice (MHV), rats (RtCoV); Manx shearwater (PCoV)

Mice (PCoV)

Type species

Betacoronavirus 1

Bovine coronavirus (BCoV); Human coronavirus OC43 (HCoV-OC43); Human enteric coronavirus (HECoV); Porcine hemagglutinating encephalomyelitis virus (PHEV); Canine respiratory coronavirus (CRCoV); Equine coronavirus (ECoV); Bubaline coronavirus (BuCoV); Giraffe coronavirus (GiCoV); Sable antelope coronavirus (SACoV); Sambaar deer coronavirus (SDCoV); Waterbuck coronavirus (WbCoV); White-tailed deer coronavirus (WtDCoV); Elk coronavirus (EkCoV)

BCoV:Mebus; DB2; HCoV-OC43:VR759;VA; PHEV:Minnesota; CRCoV:4182; BuCoV:179/07-11; GiCoV:US/OH3/2003

Cattle, humans, swine, dogs, horses, ruminants

Turkeys,dogs (BCoV); mice(HCoV-OC43);cattle(HECoV)

Approved member

Human coronavirus HKU-1 (HCoV-HKU1)

 

N5P8; Caen; LZ20

Humans

 

Approved member

Pipistrellus bat coronavirus HKU5 (Pi-BatCoV-HKU5)

 

HKU5-1 LMH03f

Bats (Pipistrellus spp.)

 

Approved member

Rousettus bat coronavirus HKU9 (Ro-BatCoV-HKU9)

 

HKU9-1 BF_005I

Bats (Rousettus spp.)

 

Approved member

SARS-related coronavirus (SARSr-CoV)

Severe acute respiratory syndrome coronavirus (SARS-CoV); Severe acute respiratory syndrome-related Rhinolopus bat coronavirus (SARSr-Rh-BatCoV); Severe acute respiratory syndrome-related Rhinolopus bat coronavirus 273 (SARSr-Rh-BatCoV-273); Severe acute respiratory syndrome-related Rhinolopus bat coronavirus HKU3 (SARSr-Rh-BatCoV-HKU3)

SARS-CoV: Urbani; Toronto; GDO3

Humans, wild carnivores (SARS-CoV); bats

Mice, hamsters, cats, ferrets, non-human primates

Approved member

Tylonycteris bat coronavirus HKU4 (Ty-BatCoV-HKU4)

 

HKU4-1 B04f

Bats (Tylonycteris spp.)

 

Approved member

Nucleotide Sequences

Genomic region

Species

Strain

Nucleotides

Access number

References

Complete genome

Murine coronavirus (MHV)

A59-C12

31,357

AF029248

Leparc-Goffart et al (1997)

Complete genome

Murine coronavirus (Rt-CoV)

Parker

31,250

NC_012936

Spiro et al (2009) direct submission

Complete genome

Ty-BatCoV-HKU4

HKU4-1 B04f

30,286

NC_009019

Woo et al (2007)

Complete genome

Pi-BatCoV-HKU5

HKU5-1 LMH03f

30,482

NC_009020

Woo et al (2007)

Complete genome

Ro-BatCoV-HKU9

HKU9-1 BF_005I

29,114

NC_009021

Woo et al (2007)

Complete genome

HCoV-HKU1

N5P8 genotype A/B

29,755

DQ339101

Woo et al (2006)

Complete genome

Betacoronavirus-1 (BCoV)

DB2

31,023

DQ811784

Spiro, et al (2006) direct submission

Complete genome

Betacoronavirus-1 (PHEV)

VW572

30,480

DQ011855

Vijgen et al. (2006)

Complete genome

Betacoronavirus-1 (SACoV)

US/OH1/2003

30,995

EF424621

Zhang et al (2007) direct submission

Complete genome

Betacoronavirus-1 (GiCoV)

US/OH3/2003

31,002

EF424623

Hasoksuz et al (2007)

Complete genome

Betacoronavirus-1 (ECoV)

NC99

30,992

EF446615

Zhang et al (2007)

Complete genome

Betacoronavirus-1 (HECoV)

4408

31,029

FJ415324

Zhu et al (2008) direct submission

Complete genome

Betacoronavirus-1 (HCoV-OC43)

87309 Belgium 2003

30,723

AY903459

Vijgen et al (2005)

Complete genome

Betacoronavirus-1 (SDCoV)

US/OH-WD388/1994

30,997

FJ425189

Alekseev et al (2008)

Complete genome

Betacoronavirus-1 (WbCoV)

US/OH-WD358/1994

30,962

FJ425186

Alekseev et al (2008)

Complete genome

Betacoronavirus-1 (WtDCoV)

US/OH-WD470/1994

31,020

FJ425187

Alekseev et al (2008)

Complete genome

SARSr-CoV (SARS-CoV)

HKU-39849

29,742

AY278491

Zeng et al (2003)

Complete genome

SARSr-CoV (SARSr-Rh-BatCoV HKU3)

HKU3-2

29,687

DQ084199

Lau et al (2005)

Complete genome

SARSr-CoV (SARSr-Rh-BatCoV 273)

BtCoV/273/2005

29,704

DQ648856

Tang et al (2006)

Genomic 3′ end

Betacoronavirus-1 (BuCoV)

Italy/179/07-11

9,679

EU019216

Decaro et al (2008)

Genomic 3′ end

Betacoronavirus-1 (CRCoV)

240/05

9,686

EU999954

Lorusso et al (2009)

N protein gene

Murine coronavirus (PCoV)

 

1,728

AJ544718

Wu et al (2003) direct submission

Proteins

Protein name

Protein name abbreviation

Number of amino acids

Molecular weight (kDa)

Time of expression

Accession numbers

Additional information

Polyprotein 1ab (replicase complex)

pp1ab

6793–7241

740–800

Throughout

AAR91584; AAP13442; ADE34721; ADE34822; ABG47068; YP_001039961; ADM33557; YP_001039952; BAF75628; YP_459949; YP_003038518; AAT84359; YP_001671996; ADI59786; YP_003029844; ABD75543

Encoded by two ORFs, 1a and 1b; pseudoknot involved in frameshifting; cleaved to several products, including an RNA-dependent RNA polymerase

Hemagglutinin esterase

HE

386–439

65

Throughout

D00764; AAT98579; AAY68296; YP_209232; ABP38257; NP_937949

Present in all members of the genus except SARSr-CoV, Ro-BatCoV-HKU9, Ty-BatCoV-HKU4, Pi-BatCoV-HKU5; non-essential

Spike glycoprotein

S

1241–1376

150–220

Throughout

AAM77000; ACJ66971; ACJ67012; AAF25499; YP_003038522; ACJ66977; CAA83661; AAQ67205; AAF69334; AAF97738; ABD75545; ABN10857; ABG47052; ADM33574; ABN10911; YP_001039962; ADE34733; ACU31051; AAV97986

Highly glycosylated; forms homotrimers; cleaved to S1 and S2 subunits

Membrane protein

M

219–230

23–25

Throughout

AF220295; ABP38308; ABG78752; AAY68301; AAT84357; AAF36439; AAD33106; ABD75508; ABN10854; YP_729208; ABN10890; ADM33569; ABD75325; ADE34793; AAP41041; AAU04653

N-linked or O-linked glycans; triple-spanning

Envelope protein

E

75–88

9–12

Throughout

AAR01017; AAM77003; NP_150081; ABG78751; YP_003029850; ACN89766; ABD75515; ABN10889; ABN10862; YP_729207; ABD75324; ACZ72168; AAP41040

Essential for virion assembly; E plus M forms virus-like particles

Nucleocapsid protein

N

417–470

50–60

Throughout

AAA66397; ACL13001; ABP38321; AAR01019; ACH72650; ABP87995; ACN89747; AAD33104; ABD75581; ABN10900; ABN10939; ABG47067; AAZ41337; ADK66848; ABN10855; AAP50495; ACZ72030

Highly basic phosphoprotein; forms a helical nucleocapsid

Non-structural protein 2a (32 kDa)

ns2a (ns2 or ns32kDA)

194–278

30–32

Throughout

AAF25507; ABV74052; ABG78746; ABP87988; AAA74377; ACN89750; AAU06354; AAF97736; YP_459950

Unique to Betacoronavirus-1 and Murine coronavirus; ns2a in murine coronavirus; ns2 or ns32kDa in Betacoronavirus-1; gene between pp1ab and HE genes

Non-structural protein 4

ns4

106–139

15

Throughout

AAF97739; YP_003029849; YP_209234; ACN89764

Unique to Murine coronavirus; two distinct ORFs (4a, 4b) in Betacoronavirus-1; not essential; may be truncated in some strains

Non-structural protein 4a (4.9 kDa)

ns4a (ns4.9 kDa)

29–44

4.9

Throughout

AAF25500; AAF25510; AAG40624; ABV74055; ACL12997; ACJ35490

Unique to Betacoronavirus-1; not essential for replication; may be truncated in some strains

Non-structural protein 4b (4.8 kDa)

ns4b (ns4.8 kDa)

43–45

4.7–4.8

Throughout

AAF25501; AAG60546; AAL40402; ACJ35491

Unique to Betacoronavirus-1; not essential for replication; may be truncated in some strains

Non-structural protein 5 (12.7 kDa)

ns5 (ns5a or ns12.7 kDa)

107–112

12.6–13.1

Throughout

AAF19390; NP_068672; AAF97740; YP_173239; YP_003038502; AAF25502; ACX46843

Unique to Murine coronavirus/Betcoronavirus-1/HCoV-HKU1; ns5 in MHV;ns12.7 kDa in BCoV; ns4 in HCoV-HKU1; not essential; may be truncated in some strains

Internal protein

I (N2)

136–220

23

Throughout

ACN89765; ACN89684; ACT11047; AAF25516; ABG78754; AAY68303; ABP87996; NP_937955; ACT11037; ABC70724

Unique to Murine coronavirus/Betacoronavirus-1/HCoV-HKU1; ORF is within the N gene; not essential; may be truncated in some strains

SARS-CoV 3a protein

Sars3a

274

30.9

Throughout

ACZ72036; ACZ72226; ACQ82726; ADE34813; ADE34734; ABD75316; AAU04635

Unique to SARSr-CoV; O-glycosylated, triple membrane spanning; forms homotetramers; not essential for replication

SARS-CoV 3b protein

Sars3b

114–154

12.8–17.7

Throughout

ACZ71978; ACB69862; ACB69907; AAU04636; YP_001382387; ABD75317

Unique to SARSr-CoV; not essential for replication

SARS-CoV 6 protein

Sars6

63

7.5

Throughout

ABA02272; ACZ72098; ACZ71861; AAP13448; AAU04639; ABD75318; ADE34737; ADE34805

Unique to SARSr-CoV; not essential for replication

SARS-CoV 7a protein

Sars7a

122

13.9

Throughout

ACQ82731; ACZ72041; ACZ72128; ACZ72216; ACZ72260; NP_828857

Unique to SARSr-CoV; type I transmembrane protein; not essential for replication

SARS-CoV 7b protein

Sars7b

44

5.3

Throughout

CAJ15124; ABA02274; ABA02274; ACZ71953; BAC81397; AAS44625; ACQ82732; AAU04656; YP_001382367; ABD75329; ADE34728

Unique to SARSr-CoV; not essential for replication

SARS-CoV 8 protein

Sars8

122–123

13.8

Throughout

AAZ67036; ABG47066; AAU04657; AAZ67036; AAV91639

Unique to some SARSr-CoVs (early human and animal SARS-CoVs); present as two distinct ORFs (8a and 8b) in human SARS-CoV due to a 29-nt deletion

SARS-CoV 8a protein

Sars8a

39

4.3

Throughout

NP_849176; ACZ72058; ACZ72277; ACZ71804; ACZ71969

Unique to most human SARSr-CoVs; originating from a 29-nt deletion in ORF8; not essential for replication

SARS-CoV 8b protein

Sars8b

84

9.5

Throughout

CAJ15126; NP_849177; ACZ72059; BAC81413; AAP41046; ACZ71805

Unique to most human SARSr-CoVs; originating from a 29-nt deletion in ORF8; not essential for replication

SARS-CoV 9b protein

Sars9b

97–98

10.8

Throughout

ACB69891; AAR87585; BAC81401; AAP69659; ACB69857; AAU04659; ADE34821; ADE34810; AAZ67037

Unique to SARSr-CoV; gene located within N gene; not essential for replication

SARS-CoV 14 protein

Sars14

70

7.8

Throughout

ACZ72047; ADC35508; ACZ72207; ACZ72032; AAU04674; YP_001382371; AAZ67042; AAZ67045

Unique to SARSr-CoV; also known as ORF10 protein; not essential for replication

Biology

Species

Permissive cell lines

Tissue tropism

Cytopathic effects

Additional information

Murine coronavirus (MHV)

Sac(−), L2, DBT, RK13, 17Cl-1

Intestine, liver, CNS

Syncytia with several cell types

Tropism is virus strain dependent

Murine coronavirus (RtCoV)

L2, LBC, RBL-02

Respiratory tract, parotid gland

Syncytia formation

Infects laboratory rats at high prevalence

Murine coronavirus (PCoV)

NCTC-1469

Skin, lung, blood

Cell rounding and detachment, syncitya formation

 

Betacoronavirus-1 (BCoV)

HRT-18, PK15, PK3, MDBK, BEK-1

Intestine, respiratory tract

Cell lysis; syncytia if trypsin present

No genetic differences between enteric and respiratory strains

Betacoronavirus-1 (HCoV-OC43)

HRT-18, MA-321, DRG-N

Upper respiratory tract

Cytoplasm vacuolisation, degeneration of monolayer

Infects astrocytes and microglial cells; some strains replicate in the enteric tract

Betacoronavirus-1 (HECoV)

HRT-18; HFI; J774; C6/36

Intestinal epithelium

Formation of giant cells and small syncytia

 

Betacoronavirus-1 (PHEV)

Pk-15, IBRS2, SK, SK-K

Intestine and CNS

Syncytia formation

Also replicates in respiratory tract

Betacoronavirus-1 (CRCoV)

HRT-18

Respiratory tract

No evident cytopathic effect

Also replicates in the intestine

Betacoronavirus-1 (ACoV)

HRT-18

Intestinal epithelium

Cell rounding and detachment

 

Betacoronavirus-1 (ECoV)

HRT-18

Intestinal epithelium

Round refractile cells, syncytia formation

 

Betacoronavirus-1 (BuCoV)

HRT-18

Respiratory tract

Syncytia formation and subsequent cell lysis

Poor growth in MDBK cells

Betacoronavirus-1 (GiCoV, SACoV, SDCoV, WbCoV, WtDCoV, EkCoV)

HRT-18

Intestinal epithelium

Rounded cells and syncytia formation

 

HCoV-HKU1

None

Upper and lower respiratory tract

Not applicable

A certain replication has been obtained using human ciliated airway epithelial cell cultures

SARSr-CoV (SARS-CoV)

Vero-E6; FRhK-4; Caco-2; LLC-Mk2; HuH7; RK-13; MA-104; CV-1

Lower respiratory tract (pneumocytes/macrophages)

Cell rounding, refractivity and cell detachment

Also grows on lymphoid cell cultures causing a non-lytic infection

Diseases

Disease

Causative agent

Affected organisms

Disease characteristics

Transmission route/vector

Treatment

Geographic distribution

Mouse hepatitis and encephalitis

Murine coronavirus (MHV)

Mice

Hepatitis, diarrhoea, acute or chronic demyelinating encephalomyelitis

Faecal-oral

None

Worldwide

Rat pneumonia and sialodacryoadenitis

Murine coronavirus (RtCoV, SDAV)

Rats

Pneumonia, rhinitis, sialodacryoadenitis

Aerosol

None

Worldwide

Puffinosis

Murine coronavirus (PCoV)

Manx shearwater (Puffinus puffinus)

Blisters on the webs of the feet, conjunctivitis and locking of the ankle joint of the legs

Likely aerosol

None

South-west coast of Wales

Bovine enteritis and respiratory disease

Betacoronavirus-1 (BCoV)

Cattle

Acute enteritis in newborns, wynter dysentery in adults, respiratory disease in all ages

Faecal-oral, aerosol

Only symptomatic

Worldwide

Human common cold

Betacoronavirus-1 (HCoV-OC43)

Humans

Common cold (sneezing, coughing, nasal discharge)

Aerosol

Only symptomatic

Worldwide

Human enteritis

Betacoronavirus-1 (HECoV)

Humans

Diarrhoea

Faecal-oral

Only symptomatic

A single case reported in the USA

swine encephalomyelitis, vomiting and wasting disease

Betacoronavirus-1 (PHEV)

Swine

vomiting, weight loss, encephalomyelitis

Faecal-oral

Only symptomatic

Worldwide

Canine respiratory disease

Betacoronavirus-1 (CRCoV)

Dogs

Cough, nasal discharge, tracheobronchitis

Aerosol

Only symptomatic

Worldwide

Equine enteritis

Betacoronavirus-1 (ECoV)

Horses

Enteritis

Faecal-oral

Only symptomatic

USA, Japan

Buffalo enteritis

Betacoronavirus-1 (BuCoV)

Water buffaloes (Bubalus bubalis)

Enteritis

Faecal-oral

Only symptomatic

Italy, Bulgaria

Alpaca enteritis

Betacoronavirus-1 (ACoV)

Alpacas (Vicugna pacos)

Enteritis, fever

Faecal-oral

Only symptomatic

USA

Wild-ruminant enteritis

Betacoronavirus-1 (GiCoV, SACoV, SDCoV, WbCoV, WtDCoV, EkCoV)

Wild ruminants (giraffes, sable antelopes, sambaar deer, waterbuck, white-tailed deer, elks)

Enteritis

Faecal-oral

Only symptomatic

USA

Human respiratory disease

HCoV-HKU1

Humans

Fever, cough, coryza, sore throat, bronchiolitis, bronchitis, pneumonia and croup

Aerosol

Only symptomatic

Worldwide

Severe acute respiratory disease

SARSr-CoV (SARS-CoV)

Humans

Flu-like prodrome, fever, dry cough, non–respiratory symptoms e.g. diarrhoea, myalgia, headache and chills/rigors

Aerosol

Symptomatic, antivirals

East Asia with further spreading to many countries

Diagnosis

Method

Species

Sample material

Detection target

References

Electron microscopy

Murine coronavirus (MHV)

Liver, brain

Particle morphology

Dumitrescu et al (1962)

DBT cell culture and immunofluorescence assay

Murine coronavirus (MHV)

Liver, brain

Viral antigens

Hirano et al (1976)

Immunoshostochemistry

Murine coronavirus (MHV)

Liver, brain

Viral antigens

Knobler et al (1981)

RT-PCR amplification of the membrane protein gene

Murine coronavirus (MHV, RtCoV)

Tissues

Viral RNA

Homberger et al (1991)

Nested PCR amplification of the nucleocapsid protein gene

Murine coronavirus (MHV)

Faeces

Viral RNA

Yamada et al (1998)

Real-time RT-PCR amplification of the membrane protein gene

Murine coronavirus (MHV, RtCoV)

Tissues, faeces, cage swipes

Viral RNA

Besselsen et al (2002)

HRT-18, MDBK or PK15 cell culture and immunofluorescence assay

Betacoronavirus-1 (BCoV, HCoV-OC43, PHEV, CRCoV, BuCoV, GiCoV, ECoV, ACoV, SACoV, WbCoV, SDCoV, WtDCoV, EkCoV)

Faeces, intestine, respiratory specimens

Viral antigens

Peterson et al (1976)

Electron microscopy

Betacoronavirus-1 (BCoV, HCoV-OC43, PHEV, CRCoV, BuCoV, GiCoV, ECoV, ACoV, SACoV, WbCoV, SDCoV, WtDCoV, EkCoV)

Faeces, intestine, respiratory specimens

Particle morphology

Chasey and Lucas (1977)

Protein A-colloidal gold immunoelectron microscopy

Betacoronavirus-1 (BCoV, HCoV-OC43, PHEV, CRCoV, BuCoV, GiCoV, ECoV, ACoV, SACoV, WbCoV, SDCoV, WtDCoV, EkCoV)

Faeces, intestine, respiratory samples

Viral antigens

Dea and Garzon (1991)

Haemagglutination using mouse or chicken erytrocytes

Betacoronavirus-1 (BCoV, HCoV-OC43, PHEV, CRCoV, BuCoV, GiCoV, ECoV, ACoV, SACoV, WbCoV, SDCoV, WtDCoV, EkCoV)

Faeces, intestine, respiratory specimens

Viral haemagglutinin

Storz et al (1992)

Monoclonal antibody ELISA

Betacoronavirus-1 (BCoV)

Faeces, intestine, respiratory specimens

Viral antigens

Thorns et al (1992)

Immunoistochemistry

Betacotonavirtus-1 (BCoV)

Paraffin-embedded, formalin-fixed intestines

Viral antigens

Zhang et al (1997)

Microimmunodot blot assay

Betacoronavirus-1 (BCoV)

Faeces, intestine, respiratory specimens

Viral antigens

Gaber and Kapil (1999)

Nested RT-PCR amplification of the nucleocapsid protein gene

Betacoronavirus-1 (BCoV)

Faeces, intestine, respiratory specimens

Viral RNA

Cho et al (2001)

Internally-controlled nested RT-PCR amplification of the nucleocapsid protein gene

Betacoronavirus-1 (BCoV)

Faeces, intestine, respiratory specimens

Viral RNA

Takiuchi et al (2006)

Real-time RT-PCR amplification of the membrane protein gene

Betacoronavirus-1 (BCoV, BuCoV, CRCoV)

Faeces, intestine, respiratory specimens

Viral RNA

Decaro et al (2008)

Nested RT-PCR amplification of the spike protein gene

Betacoronavirus-1 (PHEV)

Brain, faeces, intestine, respiratory specimens

Viral RNA

Sekiguchi et al (2004)

Real-time RT-PCR amplification of the nucleocapsid protein gene

Betacoronavirus-1 (CRCoV)

Respiratory specimens

Viral RNA

Mitchell et al (2009)

Immunofluorescence assay

Betacoronavirus-1 (HCoV-OC43)

Nasopharyngeal smears

Viral antigens

McIntosh et al (1978)

Monoclonal time-resolved fluoroimmunoassay

Betacoronavirus-1 (HCoV-OC43)

Respiratory specimens

Viral antigens

Hierholzer et al (1994)

Enzyme immunoassay

Betacoronavirus-1 (HCoV-OC43)

Respiratory specimens

Viral antigens

Hierholzer et al (1994)

Nested RT-PCR amplification of the nucleocapsid protein gene

Betacoronavirus-1 (HCoV-OC43)

Respiratory specimens

Viral RNA

Vabret et al (2001)

Real-time RT-PCR amplification of the membrane protein gene

Betacoronavirus-1 (HCoV-OC43)

Respiratory specimens

Viral RNA

Vijgen et al (2005)

Microarray using standard amplification and hybridization techniques

Betacoronavirus-1 (HCoV-OC43)

Respiratory specimens

Viral RNA

Lodes et al (2007)

RT-PCR amplification of the nucleocapsid protein gene

Betacoronavirus-1 (HCoV-OC43), HCoV-HKU1

Respiratory specimens

Viral RNA

Dominguez et al (2009)

Nested PCR amplification of the nucleocapsid protein gene

Betacoronavirus-1 (HCoV-OC43), HCoV-HKU1

Respiratory specimens

Viral RNA

Gaunt et al (2010)

Multiplex real-time RT-PCR amplification of the nucleocapsid protein gene

Betacoronavirus-1 (HCoV-OC43), HCoV-HKU1

Respiratory specimens

Viral RNA

Gaunt et al (2010)

Vero or FRhK cell culture and immunofluorescence assay

SARSr-CoV (SARS-CoV)

Respiratory specimens

Viral antigens

Ksiazek et al (2003)

Electron microscopy

SARSr-CoV (SARS-CoV)

Respiratory specimens

Particle morphology

Ksiazek et al (2003)

Nested RT-PCR amplification of the RdRp (nsp1ab) gene

SARSr-CoV (SARS-CoV)

Respiratory specimens, faeces

Viral RNA

Drosten et al (2003)

RT-PCR amplification of the RdRp (nsp1ab) gene

SARSr-CoV (SARS-CoV)

Respiratory specimens, faeces

Viral RNA

Peiris et al (2003)

Real-time RT-PCR amplification of the RdRp (nsp1ab) gene

SARSe-CoV (SARS-CoV)

Respiratory specimens, faeces

Viral RNA

Poon et al (2003)

Real-time RT-PCR amplification of the RdRp (nsp1ab) gene

SARSr-CoV (SARS-CoV)

Respiratory specimens, faeces

Viral RNA

Kuiken, et al (2003)

Real-time RT-PCR amplification of the nucleocapsid protein gene

SARSr-CoV (SARS-CoV)

Respiratory specimens, faeces

Viral RNA

Kuiken, et al (2003)

Immunohistochemistry

SARSr-CoV (SARS-CoV)

Formalin-fixed, paraffin-embedded tissues

Viral antigens

Kuiken et al (2003)

Indirect immunofluorescence assay

SARSr-CoV (SARS-CoV)

Serum

Anti-viral antibodies

Kuiken et al (2003)

ELISA test using whole virus

SARSr-CoV (SARS-CoV)

Serum

Anti-viral antibodies

Ksiazek et al (2003)

RT-PCR amplification of the nucleocapsid protein gene

SARSr-CoV (SARS-CoV)

Respiratory specimens, faeces

Viral RNA

Bermingham et al (2004)

Virus neutralising antibody test

SARSr-CoV (SARS-CoV)

Serum

Anti-viral antibodies

Zheng et al (2004)

Immunochromatographic test

SARSr-CoV (SARS-CoV)

Serum

Anti-viral antibodies

Wu et al (2004)

Western blot

SARSr-CoV (SARS-CoV)

Serum

Anti-viral antibodies

Wu et al (2004)

Dot blot enzyme-linked immunosorbent assay

SARSr-CoV (SARS-CoV)

Serum

Anti-viral antibodies

Chow et al (2004)

ELISA test using recombinant nucleocapsid protein

SARSr-CoV (SARS-CoV)

Serum

Anti-viral antibodies

Guo et al (2007)

Nucleocapsid-based human coronavirus immunoassay

SARSr-CoV (SARS-CoV)

Serum

Anti-nucleocapsid protein antibodies

Severance et al (2008)

Internally-controlled real-time RT-PCR amplification of the RdRp (nsp1ab) gene

SARSr-CoV (SARS-CoV)

Respiratory specimens, faeces

Viral RNA

Yu et al (2008)

Localized surface plasmon coupled fluorescence (LSPCF) fiber-optic biosensor

SARSr-CoV (SARS-CoV)

Serum

Viral antigens (nucleocapsid protein)

Huang et al (2009)

Surface plasmon resonance (SPR)-based biosensor

SARSr-CoV (SARS-CoV)

Serum

Anti-SARS-CoV surface antigen antibodies

Park et al (2009)

Enzyme-linked immunosorbent assay using chemiluminescence

SARSr-CoV (SARS-CoV)

Respiratory specimens, faeces

Viral antigens (nucleocapsid protein)

Fujimoto et al (2008)

Vaccine Strains

Strain

Attenuation process

Additional information

References

Betacoronavirus-1 BCoV many strains

Inactivated vaccines

Do not prevent respiratory diseases

Saif (2010)

Betacoronavirus-1 BCoV many strains

Passage in cell culture

Do not prevent respiratory disease

Saif (2010)

SARSr-CoV SARS-CoV strain Utah

Double-inactivated, whole-virus vaccine

Not yet licenced; reached the phase 1 clinical trial testing

Spruth et al (2006)

VRC-SRSDNA015-00-VP vaccine containing the spike gene of SARS-CoV strain Urbani

DNA vaccine expressing the spike protein

Not yet licenced; reached the phase 1 clinical trial testing

Martin et al (2008)

Vector Constructs

Vector name

Backbone strain

Application

Insertion capacity (kb)

Additional information

References

p25HE

Murine coronavirus MHV-JHM

Expression

1.4

Helper-dependent expression system

Liao et al (1995)

MHV-GFP

Murine coronavirus MHV-A59

Expression

0.5

Genome vector generated by recombination

Fischer et al (1997)

pMH54

Murine coronavirus MHV-A59

Reverse genetics

10.2

Used for targeted RNA recombination to obtain chimeric MHVs

Kuo et al (2000)

pJHM

Murine coronavirus MHV-JHM

Reverse genetics

10.2

Used for targeted RNA recombination to obtain chimeric MHVs

Ontiveros et al (2001)

icMHV-A59

Murine coronavirus MHV-A59

Reverse genetics

31.5

Full-length genome infectious clone constructed through ligation of seven inserts

Yount et al (2002)

icSARS-CoV

SARsr-CoV SARS-CoV Urbani

Reverse genetics

29.7

Full-length genome infectious clone constructed through ligation of six inserts

Yount et al (2003)

vMHV-inf-1

Murine coronavirus MHV-A59

Reverse genetics

31.4

Recombinant vaccinia virus containing the full-length genome of MHV

Coley et al (2005)

pBAC-SARS-CoV

SARSr-CoV SARS-CoV Urbani

Reverse genetics

30

Infectious bacterial artificial chromosome

Almazan et al (2006)

pBAC-OC43(FL)

Betacoronavirus-1 HCoV-OC43

Reverse genetics

30

Infectious bacterial artificial chromosome

St-Jean et al (2006)

Betacoronavirus-1 (BCoV). Fig. 1
figure 00571figure 00571

Transmission electron micrograph, negative staining of purified virus. Length of bar (nm): 100 (Courtesy of Dr. A. Lavazza, Istituto Zooprofilattico di Lombardia ed Emilia Romagna, Italy)

Alpha-, Beta-, and Gammacoronavirus replication cycle. Fig. 2
figure 00572figure 00572

HE protein is present only in some Betacoronaviruses (Courtesy of Dr Viviana Tarallo, Department of Veterinary Public Health, Valenzano, Italy)

Genome organization of Alpha-, Beta-, and Gammacoronavirus prototypes (A) and transcription map of Murine coronavirus MHV (B). Fig. 3
figure 00573figure 00573

Numbers above bars ORFs, L leader, UTR untranslated region, Rep replicase, (A)n poly A (Modified from Springer Index of Viruses, 1st edition, with permission)