Parvovirus B19: Difference between revisions

From MicrobeWiki, the student-edited microbiology resource
Line 19: Line 19:
Parvoviruses are among the smallest DNA containing viruses that are capable of infecting mammal hosts.<ref name=ncbi/> The virion consists of 3 proteins (NS1, VP1, and VP2) and both the positive and negative DNA strands of its singular chromosome.<ref name=ncbi/> The capsid has icosahedral symmetry, and includes 60 copies of the capsomer proteins VP1 and VP2.<ref name=ncbi/> VP2 makes up 96% of the capsid and is encoded from 3125 nt to 4786 nt (Fig 2). 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.<ref name=ncbi/><ref name=Ros>[https://www.mdpi.com/1999-4915/12/12/1463. Ros, Carlos, Bieri, Jan, and Leisi, Remo. "The VP1u of Human Parvovirus B19: A Multifunctional Capsid Protein with Biotechnological Applications" 2020. Viruses, 12(12), 1463.]</ref>
Parvoviruses are among the smallest DNA containing viruses that are capable of infecting mammal hosts.<ref name=ncbi/> The virion consists of 3 proteins (NS1, VP1, and VP2) and both the positive and negative DNA strands of its singular chromosome.<ref name=ncbi/> The capsid has icosahedral symmetry, and includes 60 copies of the capsomer proteins VP1 and VP2.<ref name=ncbi/> VP2 makes up 96% of the capsid and is encoded from 3125 nt to 4786 nt (Fig 2). 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.<ref name=ncbi/><ref name=Ros>[https://www.mdpi.com/1999-4915/12/12/1463. Ros, Carlos, Bieri, Jan, and Leisi, Remo. "The VP1u of Human Parvovirus B19: A Multifunctional Capsid Protein with Biotechnological Applications" 2020. Viruses, 12(12), 1463.]</ref>


The major nonstructural protein coded for by B19V is NS1, which is encoded by nucleotides between 435 and 2448.<ref name=ncbi/> 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.<ref name=Chen/> 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.<ref name=ncbi/>
The major nonstructural protein coded for by B19V is NS1, which is encoded by nucleotides between 435 and 2448.<ref name=ncbi/> 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.<ref name=Chen/> 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.<ref name=ncbi/><ref name=Jalali>[https://www.hindawi.com/journals/ipid/2022/1639990/. Jalali, Sedigheh, Farhardi, Ali, Dehbidi, G.R., Farjadian, Shirin, Sharifzadeh, Sedigheh, Ranjbaran, Reza, Seyyedi, Noorossadat, Namdari, Sepide and Behzad-Behbahani, Abbas. "The Pathogenic Aspects of Human Parvovirus B19 NS1 Protein in Chronic and Inflammatory Diseases" 2022. Interdisciplinary Perspectives on Infectious Diseases.]</ref>
 
Results from a study





Revision as of 20:42, 6 April 2024

Background

The life cycle of Canine Parvovirus. Photo credit: [1]

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 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]

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: [2]

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]

Morphology of B19V and Viral 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 (Fig 2). 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]

Results from a study


“Results indicated that proinflammatory cytokine levels had increased following the expression of hPVB19 NS1 in HEK-293T cells, consistent with a role for NS1 expression facilitating the upregulation of inflammatory reactions” (Jalali) Role in chronic and inflammatory diseases Previous study READ IT

INSERT IMAGE

IL17A = sig diff, role in cancer development? (Jalali) Increase of IFN and TNF in supernatants from NS1-transfected cells can induce IL-6 and shows a potential for NS1 to play a role in triggering autoimmune disorders (Jalali) B19V NS1-V9 and B19V NS1-A6 diverge by 13% from B19V NS1, but only 6% in terms of protein (Chen) B19V NS1-A6 was unable to support replication of the prototype B19V genome, but could successfully replicate and package other A6 genomes Shows NS1 has genotype-specific activity in DNA replication


There are other open reading frames, but the function of their resulting proteins is unknown -- further research?

Section 3

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

Section 4

Conclusion

References



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