Fifth Disease Causes

Fifth disease, so called because it is the fifth of the six most common infectious diseases of childhood to be historically discovered, is normally a mild illness characterized by a rash. It is also called erythema infectiosum and affects more children than adults. Most adults are seropositive and remain immune to it throughout their lives.

The infection is caused by parvovirus B19, which is a small (22-24 nm) single-stranded DNA virus lacking an envelope, belonging to the Parvoviridae family. It is the only virus in this family that causes sickness in humans. It is a common virus and causes community-acquired respiratory illness. It has only two proteins and a linear DNA molecule and is icosahedral in its morphology. The small amount of DNA, as well as the lack of envelope, confers extreme hardiness against lipid-dissolving inactivating agents so that it remains stable for one hour at 56°C. It can, however, be inactivated using formalin, gamma rays or β-propiolactone. It is difficult to culture in vitro.

Parvovirus B19 is known to be linked to a number of illnesses, ranging from very mild and self-limiting to fatal. Some of these were not causally associated with the virus until recently, leading to an underestimation of its effects. It is found across all countries and ethnicities, without regard to age, gender or socioeconomic status.

The rash from fifth disease on a child. Image Credit: Weakiva / Shutterstock

Mechanism of Illness

The parvovirus B19 targets the erythroid progenitors, that is, the cells that give rise to the red blood cells in peripheral circulation. These precursor cells are located in the bone marrow. The site of binding is the glycosphingolipid globoside (Gb4). When the virus binds to the erythroid cell receptor, very marked changes occur in the cells leading to their death, either because of cell lysis or through programmed cell death (apoptosis) in response to a cytotoxic protein called NS1.

The B19 virus is thought to suppress the production of red blood cells in all infected individuals, but this is temporary in healthy people. Thus the hemoglobin levels do not show any significant drop because of the 120-day lifespan of a typical red blood cell. The sign of this phenomenon is, therefore, the tell-tale drop in reticulocyte count, which in experiments has been found to go down to zero after one week of infection. Reticulocytes are immature red cells which have found their way into the circulation prematurely and are a marker of red cell synthesis.

Infection with the B19 virus leads to a strong immune reaction in the form of IgM antibodies, which may be found in the blood for 2-3 months following the acute stage. As the virus is cleared from the circulation the antibody levels also fall to undetectable levels, while IgG antibodies are synthesized for lifelong immunity. Adults are usually already seropositive or become so when tested over the course of a few years.

Lifecycle

Parvovirus B19 first binds to the globoside receptors of the host cell and undergoes internalization. The DNA then moves into the host cell nucleus and replicates. This is followed by transcription, leading to the assembly of 60 capsomers to form the capsid that encloses the genome. The host cell is finally lysed to release the mature virion particles, which are the infectious form.

The glycolipid globoside which binds the virus is also called the blood group P antigen and causes hemagglutination of human red blood cells. Genetic absence of the P antigen is protective against this infection.

The P antigen is also present on many other cells, such as the megakaryocytes which give rise to platelets, endothelial cells, and fetal muscle cells, but these do not allow the replication of parvovirus B19. It is thought that these cells do not allow complete transcription of the viral genome so that NS1 is produced but not the capsid. Another possibility is the interaction of the P antigen with another receptor which has not yet been found. This is perhaps supported by the absence of a strong correlation between the efficiency of binding by the virus to the cell and the level of P antigen expression. Though the P antigen does not allow clinical effects of B19 infection, it may be responsible for vertical transmission, the rash of fifth disease, or myocarditis.