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VIROLOGY - MCB 5505
VIRUS FAMILY:
REOVIRIDAE
(REO=Respiratory Enteric Orphan)
I.
DISTINGUISHING CHARACTERISTICS
A.
MEDIUM-SIZED, NON-ENVELOPED, DOUBLE-SHELLED VIRUSES
B.
THE GENOME IS SEGMENTED - EACH DS RNA IS A GENE
C.
TRANSCRIPTION AND BACK-TRANSCRIPTION OF mRNAs
D.
MANY HOSTS: PLANTS, INVERTEBRATES, VERTEBRATES
E.
A NUMBER OF HUMAN PATHOGENS: COLORADO TICK FEVER
VIRUS, HUMAN ROTAVIRUS, AND REOVIRUS STRAINS
II. STRUCTURE (FOR REOVIRUS-1)
A.
SIZE:
B.
ENVELOPE: NONE
C.
NUCLEOCAPSID 55 - 75 nm IN DIA.
1.
NUCLEIC ACID
a.
TYPE: RNA
BALTIMORE TYPE: III
b.
STRANDED: DS, SEGMENTED
c.
POLARITY: +6
d.
MOL. WT.: ~15 X 10 ; 22.4 KBP
e.
SEQ.-GENBANK AN: M24734(L1 OF REOVIRUS-1)
f.
# GENES: 10
#ORFs: 10-11
2.
GENETIC (PHYSICAL) MAP:
L1: (THERE ARE 9 OTHERS)
3854
CAP==============================================================
↓ (conservative)
CAP-------------------------------------------------------------| (19, AUG)
↓
(3822, UGA) |
λ3 PROTEIN, pλ3 (REPLICASE, 1267 aa)
3.
RNA SEGMENTS AND PROTEINS
RNA SEG. PROTEIN MW
L1
λ3
135
L2
λ2
140
L3
λ1
135
M1
M2
M3
S1
S2
S3
S4
VIRUS FAMILY:
COPIES
12
60
120
LOCATION
CORE
CORE
CORE
FUNCTION
REPLICASE
GUANYLYL TRANS.
CAPSID
μ2
μ1,μ1C
μ1c
μ3(μNS)
70
12
80,72 20
72
600
75
CORE
OUTER SHL
OUTER SHL
NONSTRUCT
CAPSID
PRECURSOR TO μ1c
OUTER CAPSID
ssRNA-BINDING
σ1
σ1s
σ2
σ4(σNS)
σ3
42
12
38
36
34
OUTER SHL
NONSTRUCT
CORE
NONSTRUCT
OUTER SHL
HEMAGGLUTININ
ENZYME?
REPLICASE
ssRNA-BINDING
ds RNA-BINDING
REOVIRIDAE
36
240
600
III. CLASSIFICATION
GENUS
ORTHOREOVIRUS
ROTAVIRUS
AQUAREOVIRUS
ORBIVIRUS
COLTIVIRUS
PHYTOREOVIRUS
FIJIVIRUS
CYPOVIRUS
ORYZAVIRUS
AND CHARACTERISTIC MEMBERS
PROPERTIES
MEMBERS
VERTEBRATES
10 SEGS. REOVIRUS-1, etc
MAMMALS
11 SEGS. HUMAN ROATVIRUS
FISH
11 SEGS. AQUAREOVIRUS-A
INSECTS, MAM. 10 SEGS. BLUE-TONGUE V
INSECTS, MAM. 12 SEGS. COLORADO TICK FEV V
PLANTS,
12 SEGS. RICE DWARF V
LEAFHOPPERS
WOUND TUMOR V
SUGAR CANE,
10 SEGS. FIJI DISEASE V
INSECTS
INSECTS
10 SEGS. CYTOPLASMIC
POLYHEDROSIS V
RICE, INSECTS 10 SEGS. RICE RAGGED STUNT V
IV.
VIRAL MULTIPLICATION
A.
ABSORPTION, PENETRATION & UNCOATING: The virus
binds to the cell surface via the hemagglutinin in the
outer capsid. The cell receptor is not known in many
cases. The virus is engulfed into coated pits. These
fuse with lysozomes and the low pH causes the outer
shell to dissociate from the inner core. The inner core
(capsid) remains intact throughout the replication
cycle.
B.
GENE EXPRESSION: The RNA replicase activity
depends on three proteins: λ3, λ2? and σ2, and a ss plusstrand is produced, which is capped and methylated by
viral enzymes in the core: λ2 and ?. The 12 singlestranded, capped mRNAs are extruded through the inner
core "pores", and are translated in the cytoplasm. The
new proteins form cores into which the 12 mRNAs assemble
by an unknown mechanism. The replicase that also inters
the new cores copies the mRNAs back to a DS genomic
RNA, which remains capped on the 5’-end of the sense (+)
strand. [The S1 mRNA is translated into two proteins, σ1
and σ1s in different reading frames. Two different start
UGAs near the 5’-end are used. The M3 mRNA is also translated
into two proteins with alternative UGAs that are inframe - pμNS
is longer than pμNSC by 20 amino acids at the N-terminus]
C.
GENOME REPLICATION: This is accomplished after
assembly of the new cores as described above.
D.
ASSEMBLY: Inner cores with their 12 mRNA
components, replicase, capping, and methylating enzymes
assemble in the cytoplasm. These new particles may also
produce mRNAs for new core assembly. After enough μ1c
is made the outer core assembles around the inner core
and proteins σ1 and σ3 seal the outer core a results in
a mature virion.
E.
BUDDING AND/OR RELEASE: Cell lysis releases new
virions after about 10 hours.
V.
CLINICAL CORRELATIONS
A.
Human Rotavirus is the most important cause of
infantile gastroenteritis in the world. There are
millions of cases each year world wide and more than one
million infant deaths each year. Electron micrographs
of stool samples are often used for diagnosis - more than
10
10 virus per ml may be present and the morphology is a
distinctive "wheel-like" virion. The virus is also
assayed by EIA, latex bead agglutination and RNA
analysis.
B.
Reoviruses infect a wide variety of animals. In
humans they are said to be "orphan" viruses, but are
suspected to have weak pathogenic activity which includes
mild URTIs and gastroenteritis.
C. The Coltivirus, Colorado tick fever virus, causes in
man a febrile dengue-like illness and can cause
encephalitis and even hemorrhagic fever; it is rarely
fatal. The virus is transmitted to man by the wood tick,
Dermacentor andersoni.
Man is an accidental host of the
adult tick; the larval and nymphal ticks transmit the
virus to wild rodents which may carry the virus for long
periods.