LECTURE 5 : SSDNA VIRUSES AND DISEASE

INTRODUCTION

▪ ssDNA – DNA can be of positive or negative sense, depending on the virus being studied.
▪ DNA must be converted to a double stranded form before synthesis of mRNA can proceed.
▪ (+) strand adeno associated virus and (-) strand minute virus of mice → These defective viruses are
almost completely dependent on co-infection with helper virus for their replication ( eg adeno or
herpes virus)
▪ First step in parvovirus replication is conversion of the genome to a double-stranded form by gap-
fill synthesis → terminal hairpin provides a base-paired 3´ OH terminus at which DNA elongation
can be initiated without the need for an RNA primer. → once achieve mechanism same poxvirus

PARVOVIRIDAE

a) Introduction
• smallest viruses (18-26 nm in diameter), naked.
• Two subfamilies: Parvovirinae (vertebrate viruses) and Densovirinae (invertebrate viruses).
• Carry either a (+) or (-) strand DNA.
• Attach to blood group P antigen on RBC, endocytosed into RBC, and transported to the nucleus
by microtubules.
• Depends on host proteins for virus replication
b) Example of parvovirus
1) Dependoviruses (replicate in the presence of a helper virus).
• adeno-associated (adenovirus as a helper virus).
• helper virus maybe of other DNA viruses. (HERPES VIRUS) → Some depend viruses may
replicate in the absence of a helper virus under certain circumstances.
• can be of valuable gene vectors, because:
➢ introduce genes into cell culture for mass production of protein.
➢ introduce genes into patients’ cells for cancer and gene disease therapy.
➢ not known to cause disease
2) Autonomous Parvovirus
• Autonomous parvoviruses: parvovirus B19 (isolated from a healthy blood donor).
➢ infect red blood cell precursors. - asymptomatic, however, may cause the fifth disease
(erythema infectiosum with “slapped cheek” appearance). –
➢ may also cause: → acute arthritis and aplastic anemia in chronic hemolytic anemia
patients. And Hyrops foetalis (transmitted from a pregnant woman to the fetus and may
kill the fetus).
 • In 2005, a new parvovirus was isolated from the nasopharyngeal aspirates of children with lower
respiratory tract infection.
• In Densovirinae (invetebrae) → formation of dense inclusions in the nucleus of the infected
cell. Some of these viruses are pathogens of the silkworm (Bombyx mori)
c) Structure
• Enclosed capsid icosahendral
• virion is roughly spherical, with surface protrusions and canyons

Parvovirus Replication

a) attachment and entry

• virion attaches to receptors on the surface of a potential host cell
• B19 virus the host cell is a red blood cell precursor and the receptor is the blood group P antige
• Enter by endocytosis from endosome into cytoplasm --. Ada microtubules and transport to
nuclear pore
b) Single stranded to double standard
• Converted to dsDNA by cell DNA polymerase → ends of the genome are double stranded as a
result of base pairing → and at the 3 end the –OH group acts as a primer to which the enzyme
binds.
c) Transcription and translation
• cell RNA polymerase II transcribes the virus genes
• The primary transcript(s) undergo various splicing events to produce two size classes of mRNA
• The larger mRNAs encode the non-structural proteins and the smaller mRNAs encode the
structural proteins
d) DNA replication
• virion assembly conversion of the ssDNA genome to dsDNA the DNA is replicated by a
mechanism called rolling-hairpin replication – replicate by leading and lagging stranded
• By DNA polymerase for replication and unwind use DNA helicase