3a

I. THE NAKED DNA & RNA VIRUSES

  • Naked DNA Virus:

    • Papillomavirus

    • Adenovirus

    • Parvovirus

    • Polyomavirus

  • Naked RNA Virus:

    • Calicivirus

    • Picornavirus

    • Reovirus

    • Hepevirus

II. THE PARVOVIRUSES

  • Smallest DNA animal viruses

  • Parvovirus B19:

    • Pathogenic for humans

    • Tropism for erythroid progenitor cells

      1. Erythema infectiosum (“Fifth disease”)

      2. Polyarthralgia-arthritis syndrome in normal adults

      3. Aplastic crisis in patients with hemolytic disorders

      4. Chronic anemia in immunocompromised individuals

      5. Fetal death

A. IMPORTANT PROPERTIES

  • Virion:

    • Icosahedral structure

    • Size: 18-26 nm in diameter

    • Composed of 32 capsomeres

  • Composition:

    • DNA (20%)

    • Protein (80%)

  • Genome:

    • Single-stranded DNA (a distinguishing characteristic, as most DNA viruses are double-stranded)

    • Linear structure

    • Size: 5.6 kb

    • Molecular Weight: 1.5-2.0 million

  • Proteins:

    • One major protein (VP2)

    • One minor protein (VP1)

  • Envelope:

    • None

  • Replication:

    • Occurs in the nucleus

    • Dependent on functions of dividing host cells

B. OUTSTANDING CHARACTERISTICS

  • Very simple viruses

  • One genus includes viruses that are replication defective and require a helper virus:

    • Parvovirus Characteristics

      • B19:

      • Tropism for RBC progenitors

      • Autonomous virus

      • 5596 nucleotides

      • AAV-2:

      • Defective parvovirus, needs a helper virus

      • 4680 bases

C. CLASSIFICATION OF PARVOVIRUSES

  • Parvovirinae: Infect vertebrates

    • Genera:

      • Erythroparvovirus - Human parvovirus B19

      • Bocaparvovirus

      • Protoparvovirus - Feline panleukopenia virus, Canine parvovirus

      • Dependovirus - Defective members (depend on helper virus)

  • Densovirinae: Infect insects

D. REPLICATION OF PARVOVIRUSES

  • Permissive Cells:

    • Only primary erythroid progenitors are known to be permissive for B19 infection

  • Cellular Receptor:

    • Blood group P antigen (globoside)

      • Expressed on mature erythrocytes, erythroid progenitors, megakaryocytes, endothelial cells, placenta, and fetal liver and heart

  • Coreceptor:

    • α5β1 integrin – believed to facilitate B19 entry

  • Dependence on Host Cell:

    • Parvoviruses are highly dependent on cellular functions for replication

  • Site of DNA Replication:

    • Viral DNA replication occurs in the nucleus

  • DNA Synthesis Capability:

    • Parvoviruses cannot stimulate resting cells to initiate DNA synthesis; they infect dividing cells using ≥1 cellular DNA polymerases

  • NS1 Protein:

    • Nonstructural protein essential for virus replication

  • Capsid Proteins:

    • Two capsid proteins present

REPLICATION PROCESS

  • Viral Entry:

    • Internalized through coated pits

  • Viral Genome:

    • Single-stranded (plus or minus) DNA

  • Conversion of Genome:

    • Single-stranded DNA is converted to double-stranded DNA by host factors and DNA polymerases present only in growing cells

  • Genome Delivery:

    • The internalized parvovirus delivers its genome to the nucleus

  • Site of DNA Replication:

    • Occurs in the nucleus

  • Transcription and Assembly

  • Virus Release:

    • Virus released by cell lysis

  • Mechanism of Lysis:

    • Through nuclear and cytoplasmic membrane degeneration

E. HUMAN DISEASES ASSOCIATED WITH B19 PARVOVIRUS

SYNDROME - HOST OR CONDITION - CLINICAL FEATURES

  • Erythema Infectiosum

    • Children: Cutaneous rash

    • Adults: Arthralgia-arthritis

  • Transient Aplastic Crisis

    • Underlying hemolysis: Severe acute anemia

  • Pure Red Cell Aplasia

    • Immunodeficiencies: Chronic anemia

  • Hydrops Fetalis

    • Fetus: Fatal anemia

F. PATHOGENESIS AND PATHOLOGY

  • Primary Targets:

    • Immature cells in the erythroid lineage

  • Major Sites of Viral Replication in Patients:

    • Adult marrow

    • Some blood cells

    • Fetal liver

  • Viral Replication Effects:

    • Causes cell death, disrupting red blood cell production

CLINICAL COURSE

  • First phase (days 6–12): Flu-like symptoms coincide with viremia

  • Second phase (day 18): Rash appears

F.1. TRANSMISSION

  • Routes of Transmission:

    • Respiratory

    • Parenterally (by blood transfusions or infected blood products)

    • Vertically (from mother to fetus)

    • High titers resistant to inactivation treatments

    • Higher prevalence of antibodies to B19 in individuals with hemophilia

F.2. MECHANISM OF SPREAD WITHIN THE BODY

  • Virus enters via upper respiratory tract, spreads through viremia, infects erythroid precursor cells, leading to:

    • Rash and arthralgia in healthy individuals

    • A mild drop in hemoglobin in normal hosts

    • Life-threatening aplastic crisis in chronic hemolytic anemia patients

G. CLINICAL FINDINGS

G.1. ERYTHEMA INFECTIOSUM (FIFTH DISEASE)

  • Occurrence:

    • Most common in early school-age children, occasionally affecting adults

  • Symptoms:

    • Fever and mild constitutional symptoms may accompany the rash, described as “slapped cheek”

  • Joint Involvement:

    • Frequent in adults, particularly in hands and knees

  • Arthropathy:

    • May persist for weeks, months, or years

  • Incubation Period:

    • 1-2 weeks, can extend to 3 weeks

  • Viremia:

    • Occurs 1 week post-incubation, lasts about 5 days

    • Illness is self-limited but impacts immunocompromised individuals and pregnant women

PHASES OF ILLNESS

  • First Phase:

    • Flu-like symptoms, coinciding with viremia and reticulocytopenia, and detection of circulating IgM-parvovirus immune complexes

  • Second Phase:

    • Erythematous facial rash, lace-like rash on limbs or trunk

    • Joint pain, symptoms may fade after 2-4 days, joint symptoms may persist longer

    • Specific IgG antibodies appear about 15 days post-infection

G.2. TRANSIENT APLASTIC CRISIS

  • Complicates chronic hemolytic anemia (sickle cell disease, thalassemias)

  • Abrupt cessation of red blood cell synthesis, evidenced by low reticulocyte count in marrow

  • Symptoms include dizziness, weakness due to lower hemoglobin or RBC production

G.3. B19 INFECTION IN IMMUNODEFICIENT PATIENTS (PURE RED CELL APLASIA)

  • Persistent infections due to chronic bone marrow suppression

  • Leads to chronic anemia with low RBCs but normal WBCs and platelets

  • Symptoms emerge during viremic phase; transfusions may be necessary

  • Common in congenital immunodeficiency, malignancies, AIDS, organ transplant patients

G.4. B19 INFECTION DURING PREGNANCY

  • Severe risk to fetus: hydrops fetalis and fetal death due to anemic conditions

  • Fetal death often occurs before the 20th week of gestation

G.5. HUMAN BOCAVIRUS & GASTROINTESTINAL INFECTIONS

  • Found commonly in children with acute wheezing, often in mixed infections and asymptomatic individuals

H. LABORATORY DIAGNOSIS

  • Most Sensitive Tests (detect viral DNA):

    • Polymerase Chain Reaction (PCR): Most sensitive

    • Probe Hybridization: Serum or tissue

    • In Situ Hybridization: Fixed tissues

  • Specimens for Isolation:

    • B19 DNA: Found in serum, blood cells

    • Bocavirus DNA: Detected in serum, saliva, tissue samples, respiratory secretion

  • Serologic Assays:

    • Determine recent and past exposure to parvovirus B19

    • B19 IgM antibody: Indicates recent infection, present for 2-3 months post-infection

    • B19 IgG antibody: Against conformational epitopes on VP1 and VP2, persists for years

    • Immunohistochemistry: Utilized to detect B19 antigens (protein) in fetal tissues and bone marrow

    • Notably difficult to grow human B19 and bocaviruses in culture

I. EPIDEMIOLOGY

  • Infections can occur year-round across all age groups, frequented by outbreaks in schools

  • Commonly seen in children; antibodies usually develop between ages 5 and 19

  • Seropositivity: Up to 60% in adults and 90% in the elderly

  • Transmitted via respiratory tract, can also be intravenous and vertical (mother to fetus)

  • Common among siblings and in school/daycare settings, as viruses are stable in the environment and may contaminate surfaces

J. TREATMENT

  • Clinical Findings and Corresponding Treatments:

    • Fifth Disease: Treated symptomatically

    • Transient Aplastic Crisis (Severe Anemia): Requires transfusion therapy

    • Human Parvovirus Infections: Commercial immunoglobulin preparations containing neutralizing antibodies

    • Human Bocavirus Infections: No specific treatment available

K. PREVENTION & CONTROL

  • No available vaccine against human parvovirus

  • Effective vaccines are available against animal parvoviruses (cats, dogs, pigs)

  • No antiviral drug therapy

  • Recommendations for prevention include:

    • Good hygienic practices: Handwashing, not sharing drinks

    • Contact precautions and thorough cleaning of patient rooms

L. SUMMARY

  • Parvoviruses represent the smallest of DNA viruses, heavily reliant on host cells for replication.

  • Parvoviruses are icosahedral, nonenveloped, with B19 and bocavirus being notable human pathogens.

  • B19 is linked to several clinical manifestations: Erythema infectiosum, polyarthralgia-arthritis in adults, aplastic crisis, chronic anemia in immunocompromised patients, and fetal death.

  • The most sensitive diagnostic test for parvoviruses is polymerase chain reaction (PCR), alongside immunochemical assays.

  • Clinical management varies by condition; transfusion may be required for severe cases, while prevention focuses on hygiene and contact precautions, as no vaccines are available for human diseases.