Parvovirus B19

The genome of human parvovirus B19 encodes four other proteins in addition to VP1 and VP2 and also some smaller proteins whose function is still unknown.[15] The most notable of these is the large nonstructural protein commonly referred to as NS1. NS1 is a multifunctional protein that has a role in binding and operating on the p6 promoter which gives NS1 the ability to control the transcription of the B19V genome. ^[16] NS1 sequence-specifically binds and cleaves DNA via restriction endonuclease activity at its N-terminus.^[17] NS1 is responsible for the regulation of certain cellular promoters including the p21/WAF1 promoter,^[18] and is thought to regulate the virus' own promoter.^[19] The 11 kDa protein encoded by the viral genome has been implicated in viral DNA replication.^[20]

The nucleotide substitution rate for total coding DNA has been estimated to be 1.03 (0.6-1.27) x 10⁻⁴ substitutions/site/year.^[21] This rate is similar to that of other single-stranded DNA viruses. VP2 codons were found to be under purifying selection. In contrast VP1 codons in the unique part of the gene were found to be under diversifying selection. This diversifying selection is consistent with persistent infection as this part of the VP1 protein contains epitopes recognised by the immune system.^{[citation needed]}

Like other nonenveloped DNA viruses,

The most recent common ancestor of the extant strains has been dated to about 12,600 years ago.^[23] Three genotypes—1, 2 and 3 -- are recognised. A recombination between types 1 and 3 gave rise to genotype 2 between 5,000 and 6,800 years ago.^{[citation needed]}

Transmission

The virus is primarily spread by infected respiratory droplets; blood-borne transmission, however, has been reported.^[24] As with all respiratory pathogens once presumed to transmit via respiratory droplets, it is highly likely to be carried by the aerosols generated during routine breathing, talking, and even singing. ^[25]The secondary attack risk for exposed household persons is about 50%, and about half of that for classroom contacts.^[6][26] Transmission can happen from a mother that has B19V infection during pregnancy. The baby can get infected by bloodstream and therefore develop a severe anemia.^[27]

Infectivity and symptoms

2 out of 10 infected people don't experience any symptoms but are still highly infective. The B19V infection starts with flu-like symptoms consisting fever, headache, runny nose, sore throat, joint pain and rash.^[28] Symptoms begin some six days after exposure (between 4 and 28 days, with the average being 16 to 17 days^[29]) and last about a week. The rash that children experience will appear after few days after the initial symptoms and can spread all over the body.^[28]

Infected patients with normal immune systems are contagious before becoming symptomatic, but probably not after.^[30] Individuals with B19 IgG antibodies are generally considered immune to recurrent infection, but reinfection is possible in a minority of cases.^[31] About half of adults are B19-immune due to a past infection.^[27]

Immunocompromised patients (organ transplant, HIV etc.) are prone to complications that affect the nerves, joints or bloodstream.^[28]

Epidemiology

A significant increase in the number of cases is seen every three to four years; the last epidemic year was 1998.^[32] Outbreaks can arise especially in nurseries and schools.

Parvovirus B19 causes an infection in humans only. Cat and dog parvoviruses do not infect humans due to animals having their own parvoviruses. There is always a possibility for a spillover. There is no vaccine available for human parvovirus B19,^[33] though attempts have been made to develop one.^[34][35]

Role in disease

Fifth disease

Fifth disease or erythema infectiosum is only one of several expressions of parvovirus B19. The associated bright red rash of the cheeks gives it the nickname "slapped cheek syndrome".^[6] Any age may be affected, although it is most common in children aged six to ten years. It is so named because it was the fifth most common cause of a pink-red infection associated rash to be described by physicians (many of the others, such as measles and rubella, are rare now).^[36]

Once infected, patients usually develop the illness after an incubation period of four to fourteen days. The disease commences with high fever and malaise, when the virus is most abundant in the bloodstream, and patients are usually no longer infectious once the characteristic rash of this disease has appeared.^[33] The following symptoms are characteristic:

• A usual brief viral prodrome with fever, headache, nausea, diarrhea.
• As the fever breaks, a red rash forms on the cheeks, with relative pallor around the mouth ("slapped cheek rash"), sparing the nasolabial folds, forehead, and mouth.
• "Lace-like, (reticular)" red rash on trunk or extremities then follows the facial rash. Infection in adults usually only involves the reticular rash, with multiple joint pain predominating.
• Exacerbation of rash by sunlight, heat, stress.

Papular purpuric gloves and socks syndrome

Teenagers or young adults may develop the so-called Papular purpuric gloves and socks syndrome. It is a

Polyarthropathy syndrome

A Danish study has links between B19 with polymyalgia rheumatica.[42]

Aplastic crisis and chronic erythroid hypoplasia

Although most patients have a decrease of

Parvovirus B19 is a cause of chronic anemia in individuals with immunodeficiency, receiving immunosuppressive therapy or with HIV infection. Treatment with intravenous immunoglobulin usually resolves the anemia although relapse can occur. Parvovirus infection may trigger an inflammatory reaction in AIDS patients who have just begun antiretroviral therapy.^[45]

Hydrops fetalis

Parvovirus infection in pregnant women is associated with

There is no routine laboratory test for B19V, but in case of the doctor is suspecting a B19V infection patient's blood will be drawn. The blood is then tested for antibodies. [27]

As of 2020, no approved human vaccine existed against parvovirus B19.^[54] Bernstein et. al. ^[35] tested in 2011 a possible candidate vaccine that was produced in insect cells. For the vaccine VP2/VP1 VLPs (virus-like particle) were used. This vaccine was approved to the I clinical phase, but was stopped due to unexplained reactions in patients. It was argued that the reaction could have been due to the PLA2 activity in VP1u. The reaction was either to the PLA2 activity releasing arachidonic acid and precursors of inflammatory mediators or the usage of insect cells. The PLA2 activity can be reduced or fully removed with site-directed mutagenesis. So this could still act as a candidate vaccine, but further research is needed.^[12]

See also

• Human bocavirus
• Erythema infectiosum

References