VIROLOGY - MCB 5505

VIRUS FAMILY: PAPOVAVIRIDAE

I. DISTINGUISHING CHARACTERISTICS
A. FAMILY NAME FROM CHARACTERISTICS OF 3 MEMBERS:
PAPILLOMAVIRUS, POLYOMAVIRUS, SIMIAN VACUOLATING AGENT.
ARE SMALL, ICOSAHEDRAL, NONENVELOPED VIRUSES.
B. GENOME IS CIRCULAR, SUPERCOILED, dS DNA PACKAGED AROUND
HISTONES – THEY REPRESENT MINIATURE MODELS FOR
EUKARYOTIC CELL DNA.
C. PAPILLOMAVIRUSES DIFFICULT TO GROW IN CELL CULTURE.
D. POLYOMAVIRUSES CAN HAVE PRODUCTIVE (LYTIC) OR NON
PRODUCTIVE (ABORTIVE) INFECTIONS – ABORTIVE INFECTIONS
LEAD TO TRANSFORMATION.
E. PAPILLOMAVIRUS GENOME REPLICATED AS EPISOMAL DNA.

II. STRUCTURE
A. SIZE: 40-55 nm
B. ENVELOPE: NONE
1. GLYCOPROTEINS:
2. OTHER PROTEINS:
3. MATRIX PROTEIN:
C. NUCLEOCAPSID
1. NUCLEIC ACID
a. TYPE: DNA BALTIMORE TYPE: I
b. STRANDED: DOUBLE, CIRCULAR
c. POLARITY:
d. MOL. WT.: 3-5 X 106 Da – 5-8 kbp
e. # GENES: 5-6 (polyomaviruses)
2. GENETIC (PHYSICAL) MAP:

POLYOMAVIRUS PAPILLOMAVIRUS
• SV40 HAS NO MIDDLE T-ANTIGEN

VIRUS FAMILY: PAPOVAVIRIDAE

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 3. CAPSID
a. SYMMETRY: ICOSAHEDRAL, T=7
b. CAPSOMERS: 72
c. SIZE: 40-55 nm
d. COMPOSITION
(1) PROTEINS VP1 = ~75% of total protein

POLYOMA PAPILLOMA
MAJOR VP1 47 kDa (360 copies) L1 57 kDa
MINOR VP2 35 kDa L2 43-53 kDa (several)
MINOR VP3 23 kDa
* VP2 contains entire sequence of VP3 plus 115 aa at the N-terminus *

(2) OTHER COMPONENTS

III. CLASSIFICATION AND CHARACTERISTIC MEMBERS *=TYPE SPECIES

GENERA PROPERTIES MEMBERS

POLYOMAVIRUS INFECT A WIDE BK VIRUS (BKV)
VARIETY OF JC VIRUS (JCV)
VERTEBRATES MURINE POLYOMAVIRUS(PyV)*
SIMIAN VIRUS 40 (SV40)

PAPILLOMAVIRUS WIDESPRED IN COTTONTAIL RABBIT -

NATURE, INFECT PAPILLOMAVIRUS (CRPV)*
BIRDS AND HUMAN “ (HPV)
MAMMALS ELEPHANT “ (EPV)
RHESUS MONKEY “ (RMPV)

IV. VIRAL MULTIPLICATION ( BASED ON POLYOMAVIRUS – SV40 )

A. ABSORPTION: 1. ANTI-VP1 Abs BLOCK BINDING.

2. SV40 RECEPTOR MAY BE MHC CLASS I ANTIGEN. 3. OTHER
RECEPTORS NOT KNOWN BUT APPEAR TO CONTAIN SIALIC ACID.
B. PENETRATION: 1. VIRIONS TAKEN UP BY ENDOCYTOSIS.
2. VIRIONS TRANSPORTED TO THE NUCLEUS.
C. UNCOATING: 1. OCCURS INSIDE NUCLEUS.
2. VP2 AND VP3 MUTANTS ARE DEFECTIVE IN UNCOATING.
D. GENE EXPRESSION: 1. ONCE INSIDE GENOME-HISTONE
COMPLEX IS TRANSCRIBED BY HOST CELL RNAP II TO PRODUCE
EARLY mRNAs. 2. VIRUS IS HEAVILY DEPENDENT ON THE CELL
FOR TRANSCRIPTION AND REPLICATION. 3. GENOME DOES HAVE
CIS-ACTING REGULATORY SIGNALS WHICH DIRECT
TRANSCRIPTION, AND TRANS-REGULATORY PROTIENS (T-
ANTIGENS)WHICH DIRECT TRANSCRIPTION AND REPLICATION.
4. ALTERNATIVE SPLICING PRODUCES SMALL, MIDDLE (NONE IN
SV40), AND LARGE T-ANTIGENS. 5. T-ANTIGEN BUILDS UP,
TRANSCRIPTION OF EARLY GENES IS REPRESSED FROM BINDING
TO ORI SITE. 6. GET SWITCH TO LATE PHASE OF INFECTION
(DNA REPLICATION THEN TRANSCRIPTION OF LATE GENES
VP1,VP2,VP3).

VIRUS FAMILY: PAPOVAVIRIDAE

E. GENOME REPLICATION: 1. INITIATED BY BINDING OF

LARGE T-ANTIGEN TO ORI SITE (CONTROLLED BY
PHOSPHORYLATION). 2. REPLICATION IS BIDIRECTIONAL FROM

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 A SINGLE ORI SITE (SIMULTANEOUSLY AT THE SAME RATE). 3.
ESSENTIAL FOR HOST CELL TO ENTER INTO S PHASE SO VIRUS
GENOME AND CELL DNA ARE REPLICATED TOGETHER (DOES NOT
HAVE ALL THE NECESSARY INFORMATION FOR DNA REPLICATION).
4. T-ANTIGEN BINDS TUMOR SUPPRESSOR PROTEINS P53 AND RB
=> CELLS ENTER S PHASE PROMOTING DNA REPLICATION.
F. ASSEMBLY: 1. VIRUS PROTEINS CONTAIN NUCLEAR
LOCALIZATION SIGNALS => MIGRATION TO AND ACCUMULATION
IN THE NUCLEUS AFTER SYNTHESIS IN CYTOPLASM. 2.
ASSEMBLY AND MATURATION OCCURS IN NUCLEUS
G. BUDDING AND/OR RELEASE: 1. SOME PARTICLES
EXPORTED TO CELL SURFACE VIA CYTOPLASMIC VACUOLES. 2.
THE REMAINING VIRUS IS RELEASED UPON LYSIS.
COMPLETE CYCLE IS ~48-72 HOURS.

* INFECTION HAS 2 OUTCOMES PRIMARILY DETERMINED BY CELL TYPE

INFECTED: 1)PRODUCTIVE (LYTIC) 2) NON-PRODUCTIVE (ABORTIVE) *

V. CLINICAL CORRELATIONS

POLYOMAVIRUSES: 1. NON-ONCOGENIC IN NATURAL HOSTS. 2.

MAJORITY OF PRIMARY INFECTIONS ARE ASYMPTOMATIC. 3.
DISEASE APPEARS TO BE ASSOCIATED WITH REACTIVATION.
JCV – ASSOCIATED WITH RARE DISEASE INVOLVING
DEMYELINATION/ INFLAMATION OF THE CNS (PROGRESSIVE
MULTIFOCAL LEUKOENCEPHYLOPATHY). BKV – PRIMARY
INFECTION ASSOCIATED WITH MILD RESPIRATORY ILLNESS IN
CHILDREN.
PAPILLOMAVIRUSES: 1. USUAL OUTCOME OF INFECTION IS
FORMATION OF A BENIGN OUTGROWTH OF CELLS (WART). SKIN
WARTS: FLAT AND PLANTAR-INCUBATION PERIOD IS 6-18
MONTHS. GENITAL WARTS (CONDYLOMAS)-INCUBATION PERIOD IS
2-6 MONTHS. WARTS MAY PERSIST OR SPONTANEOUSLY REGRESS.
2. RARE INCIDENT OF SKIN WARTS EXPOSED TO U.V. LIGHT
DEVELOPING INTO INVASIVE SQUAMOUS CELL CARCINOMA.
3. DIFFERENT KINDS OF HPV (73 GENOTYPES TO DATE) ARE
ASSOCIATED WITH DIFFERENT CLINICAL PRESENTATIONS: 95%
OF CERVICAL CANCERS CONTAIN HPV DNA PREDOMINATELY FROM
THE “HIGH RISK” TYPES (LATENCY PERIOD OVER 20 YEARS), 4.
“LOW RISK” TYPES ASSOCIATED WITH VENEREAL WARTS.
GENITAL WARTS COMPETE WITH CHLAMYDIA FOR FIRST PLACE IN
PREVALENCE AMONG SEXUALLY TRANSMITTED DISEASES.

VIRUS FAMILY: PAPOVAVIRIDAE

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 POLYOMAVIRUS PRODUCTIVE (LYTIC) INFECTION

REFERENCES

http://www.Tulane.EDU:80/~dmsander/WWW/335/Papoviruses.html

http://life.anu.edu.au/viruses/ICTdB/47000000.htm
http://info.queensu.ca/micr/micr450/papova.html

Levy, J.A., et al. (1994). Virology, 3rd ed. Prentice Hall, New
Jersey.

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