B Cell Memory Is Directed toward Conformational Epitopes of Parvovirus B19 Capsid Proteins and the Unique Region of VP1

Corcoran, Amanda; Mahon, Bernard P.; Doyle, Seán

doi:10.1086/382963

Cited by 31 publications

(19 citation statements)

References 39 publications

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“…Individuals seronegative for IgG against the unique region of VP1 have detectable B cell memory, with the potential to mount a humoral response on reexposure to B19. The finding that B cell memory is established and maintained against conformational epitopes of VP2 and against linear epitopes of VP1 but not against linear epitopes of VP2 is in accord with what observed by testing serum reactivity against diverse B19 antigens [270].…”

Section: Adaptive Immunity Antibodiessupporting

confidence: 83%

Parvovirus B19 Achievements and Challenges

Gallinella

2013

ISRN Virology

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Parvovirus B19 is a widespread human pathogenic virus, member of the Erythrovirus genus in the Parvoviridae family. Infection can be associated with an ample range of pathologies and clinical manifestations, whose characteristics and outcomes depend on the interplay between the pathogenetic potential of the virus, its adaptation to different cellular environments, and the physiological and immune status of the infected individuals. The scope of this review is the advances in knowledge on the biological characteristics of the virus and of virus-host relationships; in particular, the interactions of the virus with different cellular environments in terms of tropism and ability to achieve a productive replicative cycle, or, on the contrary, to establish persistence; the consequences of infection in terms of interference with the cell physiology; the process of recognition of the virus by the innate or adaptive immune system, hence the role of the immune system in controlling the infection or in the development of clinical manifestations. Linked to these issues is the continuous effort to develop better diagnostic algorithms and methods and the need for development of prophylactic and therapeutic options for B19V infections.

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Section: Adaptive Immunity Antibodiessupporting

confidence: 83%

Parvovirus B19 Achievements and Challenges

Gallinella

2013

ISRN Virology

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“…B19-specific IgG is detectable about 15 days postinfection and is directed initially against both linear and conformational epitopes of the capsid proteins (VP1 and VP2) and, to a lesser extent, against NS1, but declines against linear epitopes of the proteins in a time-dependent manner. Infection by B19 most likely confers lifelong protection on the host, due to the development of memory B cells that are specific for conformational regions of the B19 capsid and also linear regions of the VP1 protein (Corcoran et al, 2004). Antigen-presenting cells (APC) process the virus and display B19 peptides on their surface to Th cells.…”

Section: Cell-mediated Immunitymentioning

confidence: 99%

Advances in the biology, diagnosis and host–pathogen interactions of parvovirus B19

Corcoran

Doyle

2004

Journal of Medical Microbiology

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153

103

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Increased recognition of parvovirus B19 (B19), an erythrovirus, as a significant human pathogen that causes fetal loss and severe disease in immunocompromised patients has resulted in intensive efforts to understand the pathogenesis of B19-related disease, to improve diagnostic strategy that is deployed to detect B19 infection and blood-product contamination and, finally, to elucidate the nature of the cellular immune response that is elicited by the virus in diverse patient cohorts. It is becoming clear that at least three related erythrovirus strains (B19, A6/K71 and V9) are circulating in the general population and that viral entry into target cells is mediated by an expanding range of cellular receptors, including P antigen and â-integrins. Persistent infection by B19 is emerging as a contributory factor in autoimmune disease, a hypothesis that is constrained by the detection of B19 in the skin of apparently healthy individuals. B19 infection during pregnancy may account for thousands of incidences of fetal loss per annum in Europe, North America and beyond, yet there is currently only minimal screening of pregnant women to assess serological status, and thereby risk of infection, upon becoming pregnant. Whilst major advances in diagnosis of B19 infection have taken place, including standardization of serological and DNA-based detection methodologies, blood donations that are targeted at high-risk groups are only beginning to be screened for B19 IgG and DNA as a means of minimizing exposure of at-risk patients to the virus. It is now firmly established that a Th1-mediated cellular immune response is mounted in immunocompetent individuals, a finding that should contribute to the development of an effective vaccine to prevent B19 infection in selected high-risk groups, including sickle-cell anaemics. Parvovirus B19In 1975, Yvonne Cossart discovered what was to become known as human parvovirus B19 (B19) (Cossart et al., 1975). B19 was first associated with disease in 1981, when it was linked to an aplastic crisis in a patient with sickle-cell disease. It has since been shown to cause erythema infectiosum (EI) (fifth disease of childhood), spontaneous abortion and some forms of acute arthritis (Anderson et al., 1983; Kinney et al., 1988;Woolf & Cohen, 1995).B19 is a small, non-enveloped, ssDNA virus and, like all parvoviruses, the capsid proteins are arranged with icosahedral symmetry. B19 is 20-25 nm in diameter and has a genome of 5 . 6 kb (Clewley, 1984;Cotmore & Tattersall, 1984). The B19 capsid consists of an 83 kDa minor structural protein, VP1, and a 5 kDa major structural protein, VP2. VP2 makes up about 95 % of the total capsid, with VP1 accounting for the remaining 5 % . The sequences of the two proteins are collinear, with VP2 being identical to the carboxyl-terminus of VP1; however, VP1 comprises an additional 227 aa domain that is unique to the amino-terminal (Fig. 1). To the left of these sequences on the B19 genome is the ORF for a non-structural protein, NS1, which encodes a protein product of 7...

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“…Human sera were evaluated for HMPV IgG reactivity to the recombinant HMPV M, P, and N proteins by ELISA. Assay procedures were identical to that of Corcoran et al 31 Immunoassay cut-offs were determined as the absorbance + 2 standard deviations greater than the mean absorbance obtained from a panel of HMPV IgG negative samples (negative by ELISA and Western immunoblots to all three antigens) and an index value (I.V.) less than 1.0 was considered seronegative.…”

Section: Immunoblot and Immunosorbent Assay (Elisa) Analysismentioning

confidence: 99%

“…SAC and IL-2 jointly function to induce generalised antibody production in resting memory B cells. HMPV antigen-specific memory B cells were washed and quantified, as spot forming cells (SFC), by ELISpot technique as previously described, 31 except that HMPV antigens were used for B cell capture.…”

Section: B Cell Memory Elispot Assaymentioning

confidence: 99%

“…Memory B cells make a significant contribution to protective immunity and are characterised in terms of (i) a rapid proliferative response, accompanied by cellular differentiation upon antigen re-exposure, to produce affinity-matured, antibody-secreting plasma cells, (ii) a lower activation threshold relative to naïve B cells, in response to cytokine and antigen presence and (iii) an absence of spontaneous Ig secretion. 31 Evaluating B cell memory may have considerable importance with respect to the investigation of immunological memory to HMPV and prove useful in the elucidation of virusspecific B cell mediated immunity to HMPV.…”

Section: Introductionmentioning

confidence: 99%

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Recombinant expression and immunological characterisation of proteins derived from human metapneumovirus

O'Shaughnessy

Carr

Crowley

et al. 2011

Journal of Clinical Virology

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a b s t r a c tBackground: Human metapneumovirus (HMPV) has been shown to cause respiratory infection, accounting for approximately 7% of all such disease, and contributes to the development of asthma in humans. HMPV has a worldwide distribution with infectivity rates approaching 100%, and immunocompromised patients are particularly at risk from viral exposure. No anti-HMPV vaccine is available and diagnosis is primarily based on in-house molecular or serological tests, in part due to limited availability of recombinant HMPV antigens. Objective: To generate a panel of HMPV-derived recombinant antigens, develop standardised ELISA systems for HMPV IgG detection and explore the nature of B cell memory against HMPV to underpin future vaccine studies. Study design: HMPV viral RNA was isolated from a clinical specimen and RT-PCR was conducted. The HMPV M and P genes were cloned and expressed in Escherichia coli. The HMPV N gene was cloned and expressed in insect cells using the baculovirus expression system. Each purified recombinant antigens was subsequently employed in HMPV-specific ELISA. Results: High-level expression, and purification, of both HMPV matrix (M) (10 mg/g cells) and phosphoprotein (P) (3.82 mg/g cells) were achieved in an E. coli expression system. Recombinant HMPV (N) was successfully expressed in, and purified from the baculovirus expression system. Overall, a 99% HMPV IgG seroprevalence was observed (n = 96) using HMPV M-, N-and P-ELISA, respectively. The M antigen proved to be the most diagnostically useful with 99% of specimens tested exhibiting anti-M protein reactivity. A high correlation was observed between anti-M and N IgG reactivity (r = 0.96), with significant correlation also evident for anti-N and P IgG reactivity (r = 0.74). Lowest correlation was evident for anti-M and P IgG reactivity (r = 0.57). Finally, the first demonstration of HMPV-specific B cell memory (ranging 1-15 spot forming cells (SFC)/million cells) was achieved against M and P antigens in 40% of individuals tested. Conclusion: This work describes robust diagnostic systems for HMPV and new insight into antigen-specific B cell memory against HMPV.

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B Cell Memory Is Directed toward Conformational Epitopes of Parvovirus B19 Capsid Proteins and the Unique Region of VP1

Cited by 31 publications

References 39 publications

Parvovirus B19 Achievements and Challenges

Parvovirus B19 Achievements and Challenges

Advances in the biology, diagnosis and host–pathogen interactions of parvovirus B19

Recombinant expression and immunological characterisation of proteins derived from human metapneumovirus

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