VIROLOGY - MCB 5505

VIRUS FAMILY: CORONAVIRIDAE (CORONA = CROWN)

MEMBER OF THE NIDOVIRALES (WITH ARTERIVIRIDAE)
I. DISTINGUISHING CHARACTERISTICS
A. ENVELOPED, +STRAND RNA VIRUSES – LARGE PEPLOMERS
B. THE ONLY PLUS-STRAND VIRUSES WITH HELICAL SYMMETRY
C. LARGEST RNA GENOME (LARGEST NATURAL RNA)
D. NESTED (NIDO-) SET OF SUBGENOMIC mRNAs PRODUCED
E. PROGRAMMED FRAMESHIFT IN FIRST (LARGEST) mRNA -
2 POLYPROTEINS RESULT (2 OR 3 PROTEASES)
F. HUMAN URTIs – 25% OF COMMON COLDS
AGENT OF SARS
II. STRUCTURE
A. SIZE: 120-160 nm IN DIAMETER
B. ENVELOPE: YES
1. GLYCOPROTEINS:
S (SPIKE) PROTEIN (TRIMERS) 200 KD
M (MEMBRANE) PROTEIN
E (OR H-E) ESTERASE PROTEIN
2. OTHER PROTEINS: MAY HAVE sM (SMALL MEMBRANE)
PROTEIN
3. MATRIX PROTEIN: NONE (M PROTEIN FUNCTIONS AS)
C. NUCLEOCAPSID
1. NUCLEIC ACID
a. TYPE: RNA BALTIMORE TYPE: IV
b. STRANDED: SS
c. POLARITY: PLUS
d. MOL. WT.: 20-30 KB, 6-9 MD
e. # GENES:
2. GENETIC (PHYSICAL) MAP:

pro1 pro2 pol Zn hel

CAP-|----------------|\|--------------|-----------------------An
ORF1a ORF1b
S (200KD)
CAP---------|----------An
E
SUBGENOMIC RNAS: CAP-|------An
M
CAP--|--An
N
CAP---An
3. CAPSID
a. SYMMETRY: HELICAL
b. CAPSOMERS: NA, ?? COPIES OF N
c. SIZE: 15 X ??? nm
d. COMPOSITION:
(1) PROTEINS: N PROTEIN, ?? KD
A PHOSPHOPROTEIN
(2) OTHER COMPONENTS: NONE ??
VIRUS FAMILY: CORONAVIRIDAE

III. CLASSIFICATION AND CHARACTERISTIC MEMBERS

GENERA PROPERTIES MEMBERS

CORONAVIRUS LARGER RNA, 30KB HUMAN CORONAVIRUS
SPHERICAL, HELICAL AVIAN INF. BRONCHITIS V
MURINE HEPATITIS V
TOROVIRUS SMALLER RNA, 20KB HUMAN TOROVIRUS
DISC-SHAPED, TOROID BOVINE TOROVIRUS
EQUINE TOROVIRUS

[IN THE ORDER OF NIDOVIRALES WITH THE ARTERIVIRIDAE]

IV. VIRAL MULTIPLICATION

A. ABSORPTION. VIRUS BINDS TO SIALIC ACID RESIDUES ON
CELL GLYCOPROTEINS OR GLYCOLIPIDS OR TO HLA1 RECEPTOR.
B. PENETRATION. MEMBRANE FUSION ??
C. UNCOATING. PROBABLY UNCOATED AS A CONSEQUENCE OF
MEMBRANE FUSION THAT RELEASES THE NUCLEOCAPSID INTO
CYTOPLASM. REPLICATION OCCURS ON INTERNAL MEMBRANES.
D. GENE EXPRESSION. THE PLUS-STRAND RNA IS
INFECTIOUS. IT IS THE mRNA FOR THE PRODUCTION OF TWO
POLYPROTEINS (A PROGRAMMED FRAMESHIFT [-1] IS NECESSARY
TO PRODUCE THE ORF1b POLYPROTEIN.) WHICH ARE SELF-
CLEAVED BY TWO PROTEASES (pro1 AND pro2). THE PROTEIN
PRODUCTS ARE THE PROTEASES AND COMPONENTS OF THE RNA
REPLICASE. THE DOWNSTREAM GENES ARE EXPRESSED ON 5-7
SUBGENOMIC mRNAs. THEY ALL SHARE A 60-BASE LEADER AND
THE SAME 3’-END. ONE MODEL FOR THEIR PRODUCTION IS
FROM THE MINUS-STRAND BY A "HOPPING" MECHANISM FROM THE
LEADER TO DOWNSTREAM INTERNAL "PROMOTERS." OTHER
MODELS HAVE BEEN PROPOSED.
E. GENOME REPLICATION. A FULL LENGTH MINUS-STRAND IS
THE TEMPLATE FOR NEW PLUS-(GENOMIC)STRANDS.
F. ASSEMBLY. OCCURS ON INTERNAL (ER) MEMBRANES.
VIRAL PATCHES (MADE UP OF S AND M PROTEINS) FORM ON
THESE MEMBRANES AND VIRUS NUCLEOCAPSIDS (WHICH INTERACT
WITH M PROTEIN) BUD INTO THE LUMEN OF THE ER. VIRIONS
ARE CARRIED TO PLASMA MEMBRANE IN VESICLES WHICH FUSE
WITH THE PLASMA MEMBRANE AND EXPEL THE VIRUS.
G. BUDDING AND/OR RELEASE. AS IN F.

V. CLINICAL CORRELATIONS
A. HUMAN CORONAVIRUS CAUSES 25% OF COMMON COLDS IN
THE USA. CAN CAUSE MORE SERIOUS LRTIs. S-PROTEIN
ATTACHES TO HLA-1 RECEPTOR AND TO SIALIC ACID, THUS,
VIRUS BINDS TO MUCUS MEMBRANES. VIRUS IS CYTOPATHIC.
VIRUSES ARE NOT STRONGLY IMMUNOGENIC. TWO PROMINENT
SEROTYPES WITH NEW VIRUSES ARISING BY ANTIGENIC DRIFT.
B. THERE MAY ALSO BE AN ENTERIC CORONAVIRUS (A
TOROVIRUS) THAT CAUSES GASTROENTERITIS (DIARRHEA) IN
HUMANS.