VIROLOGY - MCB 5505

VIRUS FAMILY: TOGAVIRIDAE

I. DISTINGUISHING CHARACTERISTICS
A. SMALL ENVELOPED, +STRAND RNA VIRUSES
B. THE NUCLEIC ACID IS INFECTIOUS
C. VIRUS MATURES AT HOST PLASMA MEMBRANE, WITH
BUDDING THROUGH "VIRAL PATCHES"
D. THESE ARBOVIRUSES CAUSE ARTHROPOD-BORNE DISEASES,
INCLUDING SEMLIKI FOREST VIRUS & EASTERN
EQUINE ENCEPHALITIS VIRUS (EEE, WEE & VEE)
E. RUBELLAVIRUS (GERMAN MEASLES) IS A NON-ARTHROPOD-
BORNE TOGAVIRUS.

II. STRUCTURE (information for alphaviruses)

A. SIZE: 50-70 nm IN DIAMETER
B. ENVELOPE: YES, DERIVED FROM PLASMA MEMBRANE
1. GLYCOPROTEINS: E1 50 kb
E2 50 kb
E3 8 kb
2. OTHER PROTEINS: p62 precursor of E2 AND E3
p6K
3. MATRIX PROTEIN: NONE
C. NUCLEOCAPSID
1. NUCLEIC ACID
a. TYPE: RNA BALTIMORE TYPE: IV
b. STRANDED: SS
c. POLARITY: +
d. MOL. WT.: 4.6 MD, 12 kb
e. # GENES: 8 or 9
2. GENETIC (PHYSICAL) MAP:

49S genomic RNA

cap----------------------------------------------------------polyA
---------------------|----------|
NSP 1 2 3 4 26S subgenomic RNA
cap-----------------------polyA
C P62 6K E1
|
V
E3 & E2

3. CAPSID
a. SYMMETRY: ICOSAHEDRON, T=3
b. CAPSOMERS: 180
c. SIZE: 30-40 nm
d. COMPOSITION
(1) PROTEINS: C OR CAPSID PROTEIN
30-34 kb, 180 copies

(2) OTHER COMPONENTS: ?

VIRUS FAMILY: TOGAVIRIDAE

III. CLASSIFICATION AND CHARACTERISTIC MEMBERS

Genus Members
Alphavirus Sindbis, Simliki Forest viruses
EEE virus
Rubivirus Rubella virus
Arterivirus Equine arteritis virus
Simian hemorrhagic fever virus
Lactic dehydrogenase virus

IV. VIRAL MULTIPLICATION (based on Sinbis virus)

A. Bind by spike glycoproteins-- cell receptors are ?
B. Enters by endocytosis
C. Uncoating occurs in the cytoplasm - mechanism
unclear.
D&E. Genome serves directly as mRNA to make early
polyprotein, which is cut into three or four
proteins, nsP1 - nsP4. nsP2 has proteolytic
activity.
nsP1, 2 and 4 are RNA replicase candidates.
Minus strand accumulate briefly and then 49S
genomic and 26S subgenomic plus-strands accumulate.
49S genomic first serves as mRNA, but then is
sequestered into assembling cores in the
cytoplasm. The 26S subgenomic RNA makes all the
virion proteins, C, E1, E2 and E3 first as a
polyprotein. C protein is endoproteolytic and cuts
itself away from the E proteins, which have a
signal sequence to insert themselves into the ER.
F. Assembly of cores occurs in the cytoplasm with 180
C proteins and one 49S RNA.
G. The C protein interacts with the cytoplasmic
side of E2, which is part of a large viral patch.
Budding occurs as C proteins (of the core) pull the
E2 proteins of the viral patch around the core.

V. CLINICAL CORRELATIONS
1. Arbo virus family - mosquito- and tick-borne
EEE, Simliki Forest, others.
Encephalitis, rash fevers and hemorrhagic fevers.
EEE highly fatal to horses and man - dead-end hosts
Its natural cycle is birds <--> mosquitoes
2. Rubella virus causes German measles - crosses
placenta and infects fetus - still births and birth
defects. Air-borne transmission.