Sustained CD8
            <sup>+</sup>
            T-Cell Responses Induced after Acute Parvovirus B19 Infection in Humans

Norbeck, Oscar; Isa, Adiba; Pöhlmann, Christoph; Broliden, Kristina; Kasprowicz, Victoria; Bowness, Paul; Klenerman, Paul; Tolfvenstam, Thomas

doi:10.1128/jvi.79.18.12117-12121.2005

Cited by 43 publications

(39 citation statements)

References 30 publications

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“…The kinetics of these memory cells are reminiscent of those observed in cytomegalovirus (CMV) infection, sometimes described as memory inflation, which is also seen in parvovirus B19 infection (20)(21)(22)(23). T cell responses to both PARV4 and B19 are persistent over the years, and this finding is consistent with our previous data on a cohort of chronically HCVinfected subjects in whom PARV4 T cell responses were detected decades after the primary infection (13,24). It was previously reported that up to 4.5% of CD8 ϩ T cells responded to a specific parvovirus B19 epitope (20), while PARV4 RMTENIVEV epitope-specific T cells represented 0.1 to 1.5% of the CD8 ϩ T cells in two individuals, at levels similar to those seen for CMV or other persistent infections (25)(26)(27)(28)(29)(30).…”

Section: Discussionsupporting

confidence: 92%

Evolution of CD8 ⁺ T Cell Responses after Acute PARV4 Infection

Simmons

Levine

Bowness

et al. 2013

J Virol

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f PARV4 is a small DNA human virus that is strongly associated with hepatitis C virus (HCV) and HIV infections. The immunologic control of acute PARV4 infection has not been previously described. We define the acute onset of PARV4 infection and the characteristics of the acute-phase and memory immune responses to PARV4 in a group of HCV-and HIV-negative, active intravenous drug users. Ninety-eight individuals at risk of blood-borne infections were tested for PARV4 IgG. Gamma interferon enzyme-linked immunosorbent spot assays, intracellular cytokine staining, and a tetrameric HLA-A2-peptide complex were used to define the T cell populations responding to PARV4 peptides in those individuals who acquired infection during the study. Thirty-five individuals were found to be PARV4 seropositive at the end of the study, eight of whose baseline samples were found to be seronegative. Persistent and functional T cell responses were detected in the acute infection phase. These responses had an active, mature, and cytotoxic phenotype and were maintained several years after infection. Thus, PARV4 infection is common in individuals exposed to blood-borne infections, independent of their HCV or HIV status. Since PARV4 elicits strong, broad, and persistent T cell responses, understanding of the processes responsible may prove useful for future vaccine design. PARV4 is a small, nonenveloped single-stranded DNA virus of the Parvoviridae family that has been commonly associated with parenteral transmission (1-4). The PARV4 genome contains two open reading frames that encode a nonstructural (NS) and a capsid (VP) protein. Though PARV4 is generally absent from healthy individuals in western countries, 8 to 30% of hepatitis C virus (HCV)-infected individuals have been found to be PARV4 DNA or IgG positive (2,(4)(5)(6)(7)(8). This level can reach up to 95% among HIV-and HCV-coinfected individuals (9). Despite the growing body of evidence emerging on the prevalence of PARV4 exposure in remotely infected cohorts, relatively little is known about the features that accompany acute acquisition of PARV4 in such at-risk cohorts (3,(10)(11)(12).We previously analyzed the immune responses to PARV4 and described a striking T cell response to the NS protein in HCV ϩ and HIV ϩ individuals (13). However, this analysis was cross-sectional and the time point of infection was not known in these cases. Additionally, we were interested in studying PARV4 infection independently of other coinfections. Therefore, we subsequently sought a cohort of individuals who were HCV and HIV-1 negative but had a risk of acquiring PARV4 so that we could study acute acquisition of the virus and the evolution of immune responses in relation to viremia and seroconversion.We describe here a rare cohort of active intravenous drug users (IDUs), both HIV and HCV negative, who acquired PARV4 during the period they were under study. Because of the detailed nature of the study, with monthly follow-up over several years, it was possible to precisely identify the time of PARV4 ser...

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Section: Discussionsupporting

confidence: 92%

Evolution of CD8 ⁺ T Cell Responses after Acute PARV4 Infection

Simmons

Levine

Bowness

et al. 2013

J Virol

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“…Longitudinal studies akin to the mouse models have been somewhat hard to establish in CMV, but parvoviruses B1936, 37 and more recently PARV438, 39 can be tracked following acute infection in adults and responses to specific epitopes show similar features of delayed expansion associated with maintained effector‐memory phenotypes and sustained functionality. Parvoviruses, such as these, do not undergo a latency programme, but can establish a long‐term DNA pool in tissues, and—if the T cells are to be trusted—these data indicate long‐term epitope production.…”

Section: What Is Memory Inflation Now?mentioning

confidence: 99%

The (gradual) rise of memory inflation

Klenerman

2018

Immunological Reviews

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SummaryMemory inflation, as a term, has been used for 15 years now to describe the longitudinal development of stable, expanded CD8+ T memory pools with a distinct phenotype and functional profile which emerge in specific infection and vaccine settings. These settings have in common the persistence of antigen, especially cytomegalovirus infection but also more recently adenoviral vector vaccination. However, in contrast to chronic infections which lead to “exhaustion” the repeated antigen encounters experienced by CD8+ T cells lead to development of a robust T‐cell population structure which maintains functionality and size. In this review, I will discuss how the ideas around this form of memory have evolved over time and some new models which can help explain how these populations are induced and sustained. These models are relevant to immunity against persistent viruses, to novel vaccine strategies and to concepts about aging.

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“…Broad CD8+ T-cell responses to these epitopes were observed in acutely infected individuals and maintained or even increased over many months after the resolution of acute disease. Then, CD8+ T cells appear to play a prominent role in the control of B19V infection [274]. A discrepancy was observed in persistently infected individuals, where a comparatively higher reactivity was observed against viral capsid protein epitopes [275].…”

Section: Adaptive Immunity Cellular T-cell-mediated Immunementioning

confidence: 99%

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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Sustained CD8 ⁺ T-Cell Responses Induced after Acute Parvovirus B19 Infection in Humans

Cited by 43 publications

References 30 publications

Evolution of CD8 ⁺ T Cell Responses after Acute PARV4 Infection

Evolution of CD8 ⁺ T Cell Responses after Acute PARV4 Infection

The (gradual) rise of memory inflation

Parvovirus B19 Achievements and Challenges

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Sustained CD8 + T-Cell Responses Induced after Acute Parvovirus B19 Infection in Humans

Cited by 43 publications

References 30 publications

Evolution of CD8 + T Cell Responses after Acute PARV4 Infection

Evolution of CD8 + T Cell Responses after Acute PARV4 Infection

The (gradual) rise of memory inflation

Parvovirus B19 Achievements and Challenges

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Product

Resources

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Sustained CD8 ⁺ T-Cell Responses Induced after Acute Parvovirus B19 Infection in Humans

Evolution of CD8 ⁺ T Cell Responses after Acute PARV4 Infection

Evolution of CD8 ⁺ T Cell Responses after Acute PARV4 Infection