Parvovirus: Definition, Characteristics, and Infections

1. CHAPTER 11 Parvovirus

2. Definitions of the virus: • Parvoviruses are the causative agents of several important animal diseases. • They require cells that are passing through mitotic S phase to replicate their DNA. • Parvovirus infections are most severe in fetuses and neonates.

3. Definitions of the virus: • This requirement for mitotic active cells reflected in the tropism of parvoviruses for rapidly dividing hemopoietic precursors and lymphocytes, and progenitor cells of the intestinal mucosal lining.

4. Definitions of the virus: • The family Parvoviridae comprises two subfamilies: Paroviridae (vertebrates). • The genus Parvovirus includes feline panleukopenia virus and closely related canine parvovirus, porcine and chicken parvoviruses.

5. Definitions of the virus: • The genus Erythrovirus includes human parvovirus B19 and related viruses of non-human primates, bovine parvovirus type 3 and chipmunk parvovirus. • The genus Dependovirus includes adeno-associated viruses that are

7. Definitions of the virus: unable to replicate except in the presence of a helper virus, an adenovirus; goose and duck parvoviruses; bovine parvovirus 2. • The genus Amadovirus includes Aleutian mink disease virus; The genus Bocavirus includes bovine parvovirus and canine minute virus.

9. INTRODUCTION • Parvovirus virions are non-enveloped, 25 nm in diameter, and have icosahedral symmetry. • The capsid displays a hollow cylinder at each fivefold axis of symmetry that is surrounded by a circular depression, prominent protrusions around the threefold

10. INTRODUCTION axis of symmetry and a depression at each twofold axis of symmetry. • The capsid is composed of VP2 (90%) and approximately 10% being the overlapping but larger VP1 protein. • VP1 and VP2 are formed by alternative splicing of the same mRNA.

11. INTRODUCTION The genome consists of a linear single-stranded DNA (4.5-5.5 kbp). Individual virions of these viruses contain single-stranded DNA of either polarity. The genome contains two ORFs: an ORF in the 3’ half of the genome that encodes the non-structural proteins for DNA transcription and replication; another ORF towards 5’ half encodes the structural proteins (CAP, VP, or S) of the capsid. 11/38

12. INTRODUCTION • The entire sequence of VP2 is encoded within the VP1 gene. • A third structural protein, VP3, is formed by cleavage of a peptide from the amino terminus of VP2. • Parvoviruses are extremely stable to environmental conditions such as heat, pH, and disinfectant.

13. INTRODUCTION • The genome has terminal palindromic sequences, enabling each end to form hairpin or other complex base-paired structures. • Transferrin receptor is the receptor for canine parvovirus and feline panleukopenia virus, and it directs the virus into the clathrin-mediated uptake pathway. • Utilization of the transferrin receptor facilitates replication of these viruses which is upregulated on proliferating cells.

14. INTRODUCTION • Parvovirus replication occurs only in cells that pass through mitotic S phase. • Parvovirus binds to sialic acid residues, consistent with their ability to hemagglutinate erythrocytes of other species. • Virions traffic through the endosomal pathways within the early and late endosomes. • The VP1 protein contains a phospholipase A2 enzymes in its N-terminal region.

15. INTRODUCTION • The non-structural protein (NS1) that is encoded in the 3’ portion of the genome serves (1) attached to the 5’ end of the viral DNA during replication; (2) serves as a helicase during replication and DNA packaging; (3) serves as a site-specific nickase; (4) mediates arrest of the cell in the G1 phase. • A rolling-hairpin replication: the 3’-terminal hairpin on the negative-sense DNA genome

17. INTRODUCTION serves as a rolling-hairpin replication. • A rolling-hairpin replication: the 3’-terminal hairpin on the negative-sense DNA genome serves as a self-primer for the initiation of synthesis of a double-stranded DNA replicative intermediate. • The detection of a dimeric form of the replicative intermediate, a head-to-head concatemer of two covalently linked double-stranded forms- has led to a model in which

18. INTRODUCTION the growing DNA strand replicates back on itself to produce a tetrameric form. • The detection of a dimeric form of the replicative intermediate, a head-to-head concatemer of two covalently linked double-stranded forms- has led to a model in which the growing DNA strand replicates back on itself to produce a tetrameric form from which two complete positive or negative strands are generated.

19. INTRODUCTION • Parvovirus infections of the fetus or newborn at critical stages of organogenesis when there is considerable cell divisions may result in developmental defects. • Replication of parvovirus is restricted in hemopoietic precursors, lymphocytes, and progenitor cells of intestinal mucosa of older animals.

20. INTRODUCTION • Parvovirus infections of the fetus or newborn at critical stages of organogenesis when there is considerable cell divisions may result in developmental defects. • Replication of parvovirus is restricted in hemopoietic precursors, lymphocytes, and progenitor cells of intestinal mucosa of older animals.

21. INTRODUCTION • Many parvoviruses cause acute infections that last only a few days, others persist for long periods in the faeces of apparently robust host immune responses. • Disease develops in persistently infected mink as a result of the high levels of circulating antigen-antibody complexes that deposit in tissues and initiate a type III hypersensitivity reaction that results in tissue injury and destruction.

23. Circovirus

24. DEFINITION • The family Circoviridae includes viruses with circular single-stranded DNA genomes, and which share common physicochemical and genomic properties. • The family contains two genera (Circovirus and Gyrovirus). • Circovirus uses an ambisense genome strategy, with viral genes in different orientations.

25. DEFINITION • The genus Circovirus includes beak and feather disease virus, canary circovirus, goose circovirus, pigeon circovirus, and porcine circoviruses 1 and 2. • Chicken anemia virus is the type member of the genus Gyrovirus, in which the viral genes are all in the same orientation.

27. INTRODUCTION • They are small (approximately 20-25 nm in diameter), non-enveloped, spherical in outline, with T=1 icosahedral symmetry. • Virions are made up of 60 capsid subunits that package the viral circular single-stranded DNA. • Chicken anemia virus has 12 trumpet-like structures that are less obvious in the other circoviruses.

28. INTRODUCTION • Mature virions appear in diagnostic specimens and in linear “strings of pearls” in cell-free diagnostic specimens. • Beak and feather disease virus, porcine circovirus 1 and 2, and the other members of the genus Circovirus utilize an ambisense transcription strategy-some genes are encoded in the viral sense DNA and others in the

29. INTRODUCTION • Mature virions appear in diagnostic specimens and in linear “strings of pearls” in cell-free diagnostic specimens. • Beak and feather disease virus, porcine circovirus 1 and 2, and the other members of the genus Circovirus utilize an ambisense transcription strategy-some genes are encoded in the viral sense DNA and others in the

30. INTRODUCTION complementary strand. • Beak and feather disease virus has three ORFs and porcine circovirus has four; in each case there is one major capsid protein. • The genes of chicken anemia virus are all encoded in the complementary positive-sense DNA strand that is transcribed to give a single polycistronic transcript.

31. INTRODUCTION

32. INTRODUCTION

33. INTRODUCTION • Chicken anemia virus has three ORFs; one encodes the VP1 (present in virions); another virus-encoded VP3, apoptin, induces apoptosis of T lymphocytes. • These viruses are stable ; not inactivation by heating. • CAV hemagglutinate RBC and binds to sialic acid on the cell surface.

34. INTRODUCTION • Viral DNA replication occurs in the nucleus and requires cellular proteins and other components produced during the S phase. • Replication of the genome occurs via a rolling circle that originates at a stem-loop structure. • The viral replication is maximized in actively dividing cells in young animals.

35. INTRODUCTION • Viral DNA replication occurs in the nucleus and requires cellular proteins and other components produced during the S phase. • Replication of the genome occurs via a rolling circle that originates at a stem-loop structure. • The viral replication is maximized in actively dividing cells in young animals.

36. INTRODUCTION • Replication of porcine circovirus is enhanced during periods of immune stimulation that result in proliferation of lymphocytes in which virus can replicate. • CAV replication in the oviduct may be regulated by estrogen, particularly during egg laying, to allow more efficient vertical transmission.

37. INTRODUCTION • Replication of porcine circovirus is enhanced during periods of immune stimulation that result in proliferation of lymphocytes in which virus can replicate. • CAV replication in the oviduct may be regulated by estrogen, particularly during egg laying, to allow more efficient vertical transmission.

38. INTRODUCTION • The apoptin causes destruction of infected lymphocytes and promotes a relative immune suppression that favors virus persistence.