Parvovirus B19: Difference between revisions

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==Section 4==
==Potential Use in Development of New Treatments==


==Conclusion==
==Conclusion==

Revision as of 02:14, 8 April 2024

Background

By Grace Potter

Parvovirus B19 is the only member of the Parvoviridae family that has been found to infect human hosts.[1] It was discovered in 1974, when a research group looking at hepatitis B surface antigens found a serum sample with unexpected results.[1] Another lab in Japan described a similar virus in 1979 that they called "Nakatami".[1] When compared, the two were found to be identical.[1] In 1985 this virus was officially recognized as a member of the Parvoviridae family due to its similarities in genome size and density.[1]

Infection by Parvovirus B19 (Parvo B19V) causes many diseases, including "fifth disease" in children, aplastic crisis for people with hemolytic anemia, anemia in immunocompromised patients, acute or chronic arthropathy in adults, and fetal hydrops in pregnant women.[2][3] Changes in the genome are potentially responsible for the wide variation of clinical presentations associated with B19V infection.[2]

Parvoviruses are classified in reference to what type of host they are capable of infecting and how they reproduce.[1] Those capable of infecting vertebrate hosts are referred to as "Parvovirinae" and are further subdivided by reproduction processes.[1] "Parvovirus" refers to members of the Parvoviridae family that reproduce autonomously, but there are also members of this family seen reproducing with a helper virus, "Dependovirus", and preferentially in erythroid cells, "Erythrovirus".[1] Parvovirus B19 has recently been found to exhibit extreme specificity for human erythroid progenitor cells, and has therefore been classified as an "erythrovirus".[4][1]

Genome Structure

The V9 (A) and A6 (B) genomes are depicted with transcriptional landmarks. These include promoters (ie. P6), splice donors (D), and splice acceptors (A), as well as the ORFs encoded and their predicted protein sizes in kDa. Photo credit: [1]

The Parvovirus genome is a single strand of DNA with 5,596 nucleotides, 4,830 of which are coding regions.[1] This region contains 2 large open reading frames.[1] One large non-structural protein is coded by one open reading frame, NS1, and the second reading frame codes for 2 capsid proteins, VP1 and VP2.[1] The sequences of B19V isolates do not exhibit much genetic variation with NS1 showing incredibly high conservation, and 2-3% divergence in VP1 and VP2 regions.[1] When examining isolates from patients with chronic infection due to B19V, there is a much higher degree of variation at DNA and protein levels.[3]

There are now 3 distinct genotypes recognized as Parvovirus B19 including: (1) all prototype B19V isolates, (2) A6 and LaLi isolates, and (3) V9 and related isolates.[2] These variations in the genome are potentially responsible for the variety of host responses to infection.[2] In a study on 3 isolates of the 3 genotypes, the A6 isolate did not produce R5, R7, and R9 mRNAs, which are important in the production of VP1 and VP2 as coordinating mRNAs.[2] There was also an increase in sequence divergence between the 3 isolates. They found that B19V NS1-V9 and B19V NS1-A6 diverge by 13% from B19V NS1, but only diverge by 6% in protein structure.[2]

B19V's Essential Proteins

Parvoviruses are among the smallest DNA containing viruses that are capable of infecting mammal hosts.[1] The virion consists of 3 proteins (NS1, VP1, and VP2) and both the positive and negative DNA strands of its singular chromosome.[1] The capsid has icosahedral symmetry, and includes 60 copies of the capsomer proteins VP1 and VP2.[1] VP2 makes up 96% of the capsid and is encoded from 3125 nt to 4786 nt. VP1 is the minor capsid protein encoded from 2444 nt to 4786 nt. The VP1 coding region is identical to VP2 except for an additional 227 amino acids referred to as the VP1 unique region, or VP1u.[1][5]

The major nonstructural protein coded for by B19V is NS1, which is encoded by nucleotides between 435 and 2448.[1] NS1 is thought to contain a DNA binding domain at the N-terminus with conserved motifs for single-strand nickase and an ATP/helicase domain in the center, and a transcription activation at the C-terminal.[2] For a long time the role of NS1 in infection was largely unknown, but recent studies have highlighted its potential in the proliferation of chronic symptoms related to Parvovirus B19V infection.[1][6]

The level of expression of 8 proinflammatory cytokines after 24, 48, and 72 hours in cells transfected with a B19V NS1 vector. Significant increases in expression were seen in IL-17A and TNF-α (p<0.0006).[6] Photo credit: [2]

Results from a study indicate that the transfection of hPVB19 NS1 into HEK-293T cells increased proinflammatory cytokine levels.[6] This is consistent with the findings that NS1 might play a role in facilitating the upregulation of inflammatory reactions, including chronic arthritis which can be a symptom of chronic B19V infection.[6]

The figure to the right indicates a significant increase in the expression levels of the cytokines IL-17A and TNF-α. An increase in IFN and TNF in supernatants from NS1-transfected cells can induce the expression of IL-6, an important proinflammatory cytokine, and shows the potential of NS1 in triggering autoimmune disorders.[6] Further research is needed to fully understand the impact of NS1 on autoimmune disorders, especially considering its impact on proinflammatory cytokines.

Differences in the NS1 proteins found across the 3 genotypes of Parvovirus B19 show that B19V NS1-V9 and B19V NS1-A6 diverge by 13% from B19V NS1 in genetic sequence, but only diverge by 6% in protein structure.[2] The inability of B19V NS1-A6 to replicate the prototype B19V genome in comparison with its ability to replicate and package other A6 genomes, shows that the NS1 protein has genotype specific activity.[2]

There are other open reading frames, but the function of their resulting proteins is largely unknown.[1] Further research is needed in this area.

Pathogenesis and Infection

Include some current research, with at least one figure showing data.

Potential Use in Development of New Treatments

Conclusion

References



Authored for BIOL 238 Microbiology, taught by Joan Slonczewski,at Kenyon College,2024