POX VIRUS

Mukund S. Vats
Introduction
• Small pox caused devastating epidemics worldwide.
• However, in October 1977, after vigorous efforts by
the WHO, this disease became the first ever to be
completely eradicated.
• Pox viruses are most commonly spread by direct contact.
• However, in the case of small pox, when the virus is
found in lesions in the upper respiratory tract, can be
transmitted to others in droplet secretions.
• Infection by a pox virus results in cell-mediated
immunity.
• People who are infected with small pox are generally
immune to the disease for the rest of their lives.
Biology
• Are the largest and most complex of all viruses.
• Virion size of 220-350 x 115-260 nm.
• Can be seen under a light microscope.
• 2 subfamilies:
I. Chordopoxvirinae – Virus of chordates
II. Entomopoxviridae – Virus of insects
• Chicken pox virus does not belong this family!
- It is a herpesvirus
Classification of Poxviridae
Biology
• Genome: double-stranded
DNA, linear, noninfectious, 191
Kbp with hairpin loop end.
• Morphology: "complex“ or
brick-shaped
• Envelope: May be Enveloped
or nacked
• Replication: takes place in
cytoplasm
• Host range: host range varies
• Oncogenicity: may cause
benign tumors
• Two forms
1. Intracellular mature virion
(IMV)
2. Extracellular enveloped
virion (EEV) Generally has
extra envelope
Genome
• More than 200 genes
• The gene coding sequences are
densely packed, and the
template for RNA synthesis may
be present in either strand.
• The sequences encoding
structural proteins and essential
enzymes are clustered in
roughly the central 120 kb.
• Genes encoding virulence
proteins, hostrange proteins, or
immunomodulators are found
predominantly near the ends.
Replication
• The replication cycle of
poxviruses occurs in the
cytoplasm of the cell and
varies greatly in duration.
• It takes between 12 and 75 h
from the time of infection.
• The majority of information
concerning the replication of
poxviruses has been obtained
by using vaccinia virus.
Virus Entry into Cells
• Electron-micrographic evidence,
• In the Lysosome
• Low-pH-dependent endosomal fusion
• Enveloped virus also fuses in a pH-independent manner
with the plasma membrane, although the kinetics is more
rapid than for nonenveloped virus
• Virion to undergo at least two discrete stages of
disassembly on entry into the cell.
1. loss of outermost virion proteins and lipid
2. Uncoating of genome.
Early Gene Expression
• Almost immediately on entry into
the cell, the virion associated
transcriptional machinery is
activated and synthesizes a class of
capped and polyadenylated virus-
specific transcripts which are
homologous to approximately 50%
of the genome.
• These early gene products are
involved in interactions with the
host and in DNA.
• A DNA polymerase along with
several other protein required for
replication have been shown to be
expressed.
• These also effect the cell cycle
control, and/or form a nuclear site
of action.
DNA Replication
• Poxvirus replication is independent
of the host nucleus in discrete areas
of the cytoplasm called factories or
viroplasm,
• when observed by light microscopy,
as a discrete structure which is
referred to as a B-type inclusion
body (BTI).
• The onset of DNA replication varies
among poxviruses; it may occurs
between 2 and 5 h postinfection
with the production of ca. 10,000
genome copies.
• Recombination occurs at high levels
in poxvirus-infected
• cells and appears to be tightly linked
in DNA replication.
Late Gene Expression
• Pox viruses have 3 phases of expression.
x Early Expression
x Intermediate Expression.
x Late Expression.

• The intermediate expression is done using newly

synthesized DNA as template. It sometimes requires few
cell protein interaction as well.
• These expressed proteins activate expression of late
genes.
Virions Exit & Spread
• Generally are released upon cytolysis.
• Some species (cowpox, ectromelia, raccoonpox, skunkpox, volepox)
also occlude virions within cytoplasmic acidophilic-type inclusion
(ATI) bodies, which may be protective.
• Poxviruses also have a method of viral dissemination from the cell in
which a small proportion of IMVs become wrapped in an additional
lipoprotein layer and released as extracellular enveloped virions
(EEVs).
• Additionally, poxviruses may spread by enabling cell - cell fusion.
References
1. Chapter 27, Poxvirus Dna Replication,paula Traktman, DNA
Replication In Eukaryofic Cells, 1996 Cold Spring Harbor Laboratory
Press 0-87969-459-9/96.
2. Discovery Of Antivirals Against Smallpox, Stephen C. Harrisona, PNAS
Vol. 101, No. 31, August 3, 2004 11178–11192
(Ww.Pnas.Orgcgidoi10.1073pnas.0403600101)
3. Poxvirus Pathogenesis R. Mark L. Buller, Microbiological Reviews, Mar.
1991, P. 80-122 0146-0749/91/010080-43.