Parvoviruses

A Presentation By G. Prashanth Kumar

Department of Microbiology & Parasitology,International Medical & Technological University,

Dar-Es-Salaam, Tanzania.

INTRODUCTION• Parvoviruses are the smallest of the DNA viruses

belonging to the family Parvoviridae. • They are icosahedral, nonenveloped viruses containing a

single-stranded DNA. • Human parvovirus B 19 (B 19) is the only known

parvovirus that is pathogenic for humans, and it shows tropism for erythroid progenitor cells.

• History: In 1974, Cossart et al. first identified B19 while evaluating tests for hepatitis B virus surface antigen. The name originates from the coding of a serum sample, number 19 in panel B, that gave anomalous results when tested by counterimmunoelectrophoresis and radioimmunoassay.

Classification • The family Parvoviridae consists of three genera: • Dependo-virus, Parvovirus, and Erythrovirus. • The genus Dependovirus consists of poxviruses which are defective

and replicate only in association with a second helper virus. • They neither cause illness by themselves nor alter the infection

caused by helper viruses. • These are usually found in association with an adenovirus, hence

are known as adeno-associated viruses. • These viruses do not cause any disease in humans. • The genus Parvovirus includes the viruses which include animal

viruses of veterinary importance such as feline panleukopenia virus and canine parvovirus.

• The genus Erythrovirus consists of B 19, the only member of the Parvoviridae family known to cause disease in humans.

PARVOVIRUS B19 • Parvovirus B19, or B19 virus, is the causative agent of

erythema infectiosum ('fifth disease'-it was fifth of the six classified exanthematous diseases of childhood), a mild viral illness of children, and polyarthralgia-arthritis syndrome in immunocompetent adults.

Human infections caused by B19 virus

Morphology • B 19 viruses are extremely small

viruses, measuring 18-26 nm in diameter.

• They possess a nonenveloped, icosahedral capsid.

• The viral genome contains a single-stranded DNA measuring 4000-6000 bases in length.

• The genome is negative-strand DNA. • The genome encodes for many

proteins which include three structural, one major nonstructural, and several smaller proteins.

Viral replication • B 19 virus shows tropism for (a) bone marrow cells, (b)

erythroid cells from fetal liver, and (c) erythroid leukemia cells.

• Replication of virus occurs in the nucleus. • The single- stranded DNA genome has hairpin loops at

both of its ends which facilitate double-stranded areas for the cellular DNA polymerase to start synthesis of the progeny genomes.

• The cellular RNA polymerase synthesizes viral mRNA from the double-stranded DNA intermediate.

• This is followed by assembly of virions in the nucleus. • Viral replication results in the cell death.

Antigenic properties • Only one serotype of B 19 virus is known to occur.

Other properties • B 19 virus is highly resistant to inactivation but can be

inactivated by formalin, beta propiolactone, and oxidizing agents.

• The viruses withstand heating at 56°C for 30 minutes and are stable between pH 3 and 9.

Pathogenesis and Immunity • B 19 virus shows a tropism for two types of cells: • (a) red blood cell (RBC) precursors and • (b) endothelial cells in the blood vessels. • The virus infects rapidly dividing erythrocyte precursors such

as bone marrow cells, erythroid cells from fetal liver, and erythroid leukemia cells and destroys these cells after infection, thereby causing aplastic anemia.

• Infection of the endothelial cells in the blood vessels leads to erythema infectiosum.

• It has been demonstrated that the B19 virus first enters through the nasopharynx or upper respiratory tract and then spreads to the blood, causing viremia.

• The virus then infects mitotically active erythroid precursor cells in bone marrow and establishes the infection.

Pathogenesis and Immunity • The virus enters susceptible cells through the P blood

antigen receptors on the erythrocyte precursors. • Inside the red cells the virus enters the nucleus, starts

replicating, followed by killing of the red cells. • The production of RBCs is stopped for approximately 1

week due to killing of the erythroid precursor cells by the viruses.

• The initial stage is associated with flu-like illness caused by large viremia.

• The viruses are shed in the oral and respiratory secretions and even cross the placenta.

• Subsequently, viremia is controlled by the production of specific antibodies against B 19 virus.

Pathogenesis and Immunity • The rash and arthralgia present the second stage of the disease,

and is believed to be immunologically mediated. • This stage coincides with the disappearance of B 19 virus from

the circulation, appearance of B19 virus-specific IgM and IgG antibodies, and finally the formation of immune complexes.

Host immunity • “The disease exhibits two stages: initial stage is flu-like illness

and second stage is appearance of rash and arthralgia. • Host immunity to B 19 virus infection is primarily antibody

mediated. • The circulating antibodies stop the viremia and are important for

resolution of the disease. • The role of cell-mediated immunity in conferring immunity to B

19 virus is unknown.

Clinical Syndromes • B19 virus causes following clinical syndromes: • (a) Flu like illness, (b) erythema infectiosum or fifth disease, (c)

infection in pregnant women, and (d) chronic B 19 infection.

Flu-like illness • B 19 virus most commonly causes a flu-like illness. • Malaise, headache, myalgia, and rhinorrhea are the common

symptoms.

Erythema infectiosum or fifth disease • B 19 virus is an additional causative agent of erythema

infectiosum or fifth disease, the condition seen most commonly in children.

• The infection begins with nonspecific symptoms, followed by appearance of a distinctive rash on 5th day of infection.

Clinical Syndromes

• A bright red rash develops on both cheeks that appear as they have been slapped.

• The rash then appears on the trunk, which spreads gradually toward the arms and legs.

• The condition usually subsides within 1-2 weeks.

Clinical Syndromes

Aplastic anemia• Transient but severe aplastic anemia

can occur in children with chronic anemia such as sickle cell anemia, thalassemia, and spherocytosis (aplastic crisis) after infection with B 19 virus. Gloves and sock syndrome is another serious complication caused by B19 virus.

• In this syndrome, erythematous exanthema appears on the hands and feet, with a well-defined margin on the wrist and ankle joints.

Gloves and sock syndrome

Clinical Syndromes

Infection in pregnant women • If the B 19 virus causes reinfection in a pregnant mother

who is infected earlier by the same virus, and is already immune to the virus (showing positive B19 antibodies), then no adverse effects are seen in the fetus.

• In non immune seronegative pregnant mothers, B19 virus infection is increasingly associated with risk for fetal death.

• The infection may cause severe anemia in the fetus, and subsequently, the fetus may develop signs of high-output cardiac failure (hydrops fetalis).

• B19 virus, however, does not cause any congenital anomalies in the fetus.

Clinical Syndromes

Chronic B19 infection • This infection occurs in immunocompromised

patients such as patients with HIV, those receiving immunosuppressive therapy, and transplant patients.

• Chronic anemia, leukopenia, and thrombocytopenia are the common manifestations.

Epidemiology • Geographical distribution • B 19 virus is distributed worldwide. • The exact data on sero-positivity in population world

over is not known. • Approximately, 90% of adults older than 60 years are

seropositive in the United States. • Similar data from other parts of the world are lacking. • Reseruoir, source, and transmission of infection • B 19 virus infection is strictly a human disease. • Humans are the only reservoir of infections. Viruses are

excreted in respiratory samples which are the primary source of infection.

Epidemiology • The infected patient is contagious from 24 to 48 hours

before developing prodromal syndrome till the appearance of rash.

• The infection is transmitted by • (a) vertical transmission during birth, • (b) respiratory route through respiratory secretions, • (c) percutaneous exposure to blood and transfusion of

blood and blood products (pooled RBCs, platelets, intravenous immunoglobulins, etc.).

Laboratory Diagnosis • Demonstration of specific IgG and IgM antibodies in the

serum is useful for diagnosis of erythema infectiosum caused by B19 virus.

• ELISA (enzyme-linked immunosorbent assay), RIA (radioimmunoassay), and IFA (indirect fluorescent antibody) for demonstration of IgG and IgM antibodies are available.

• In pregnant women, the serum positive for IgG and IgM antibodies indicates B19 virus infection within 7 days to 4 months, and a possible risk to fetus.

• Positive IgG but negative IgM result indicates only past infection, hence no risk to fetus.

• Furthermore, polymerase chain reation (PCR) is available to demonstrate B19 virus genome in the blood.

• The positive result suggests viremia or infection.

Treatment • No specific antiviral therapy is available for treatment

of B 19 virus infection.

Prevention and Control • No specific measures are available for prevention of

the infection. • Development of a vaccine against B 19 virus is

undergoing phase I clinical trial.