Measles Virus Infection of Human T Cells Modulates Cytokine Generation and IL-2 Receptor Alpha Chain Expression

Bell, Amie F.; Burns, James; Fujinami, Robert S.

doi:10.1006/viro.1997.8577

Cited by 20 publications

(9 citation statements)

References 15 publications

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“…MV infection suppresses T-lymphocyte proliferation to mitogens (71,140), IL-2 responses (12,39,129), and associated downstream signaling (7,8), antigen presentation (69), and cytotoxic function (17). MV-induced suppression of B-lymphocyte maturation (73) and impaired immunoglobulin production (17, 52, 71, 120) have been described, previously.…”

Section: Proposed Mechanisms Of MV Immunosuppressionmentioning

confidence: 99%

Immune Containment and Consequences of Measles Virus Infection in Healthy and Immunocompromised Individuals

Permar

Griffin

Letvin

2006

Clin Vaccine Immunol

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2The pathogenicity of measles virus (MV) is intimately linked to the immune status of the infected individual. Measles is typically a self-limiting disease; however, individuals who are immunocompromised (56,79), malnourished (26,78,113), or at the extremes of age (23) are at increased risk for severe measles. At the present time, with human immunodeficiency virus (HIV) and immunosuppressive drug therapy affecting the immune competence of large numbers of individuals, MV is reemerging as an important pathogen worldwide. Elucidating the mechanism by which the immune system controls MV infection and prevents reinfection will be crucial for our understanding of disease pathogenesis and transmission as well as the development of novel MV vaccination strategies.Despite reaching global measles vaccination coverage of Ͼ80% of individuals, MV remains the fifth leading cause of death and the most common cause of vaccine-preventable death in children under 5 years of age (84). An estimated 31 million cases of measles occurred globally in 2001, resulting in 777,000 deaths, the majority (452,000) of which occurred in sub-Saharan Africa (84). MV is one of the most contagious pathogens known to humans, and large measles outbreaks, facilitated by overcrowding in poor communities, continue to occur even in countries that have achieved high vaccine coverage.MV is a 15-kilobase, enveloped, negative-strand RNA virus and a member of the Morbillivirus genus of the Paramyxoviridae family. MV infects only humans and nonhuman primates. It is a stable, monotypic virus, making it an excellent candidate for eventual eradication. In culture, MV can be adapted to grow in nonprimate cells, a process that has facilitated the attenuation of viral strains for the development of a safe vaccine. Measles is transmitted via direct person-to-person contact and causes a symptomatic viral prodrome culminating in the hallmark maculopapular measles rash. The measles rash is preceded by systemic viremia and lymphopenia, and clearance of the rash is followed by a transient suppression of T-lymphocyte responses that lasts several weeks, leaving the infected individual susceptible to other infections.While nonspecific innate immune mechanisms may be important in the control of MV during the first days following infection, adaptive MV-specific immune responses mediate viral clearance and provide protection against subsequent MV infections. Natural MV infection generates long-lasting immunity that includes both MV-specific antibody (14) and memory T-lymphocyte (50, 123, 136) responses. Long-term protection from reinfection occurs without a requirement for reexposure (98).This article reviews our current understanding of the immune control of MV and the consequences of MV infection on the immune system of the immunocompetent host. We then discuss the clinical consequences of MV infection in immunocompromised individuals. Finally, we describe recent studies that have raised questions regarding the outcome of MV infection in the immunocompromised host. IMMUNE CO...

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Section: Proposed Mechanisms Of MV Immunosuppressionmentioning

confidence: 99%

Immune Containment and Consequences of Measles Virus Infection in Healthy and Immunocompromised Individuals

Permar

Griffin

Letvin

2006

Clin Vaccine Immunol

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“…For example, priming with DNA-priming and boosting with recombinant vaccinia virus was the only effective regimen in some studies [104,105]. This might be due to viral products that are immunosuppressive such as soluble, secreted cytokine receptor homologues, the expression of which could interfere with immune priming, especially to weak antigens [107][108][109][110]. Furthermore, epitopes derived from viral vectors can be immunodominant over weak antigens.…”

Section: Heterologous Prime-boost-regimens Can Enhance the Efficacy Omentioning

confidence: 99%

DNA and RNA-based vaccines: principles, progress and prospects

Leitner

Han

Restifo

1999

Vaccine

345

229

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DNA vaccines were introduced less than a decade ago but have already been applied to a wide range of infectious and malignant diseases. Here we review the current understanding of the mechanisms underlying the activities of these new vaccines. We focus on recent strategies designed to enhance their function including the use of immunostimulatory (CpG) sequences, dendritic cells (DC), costimulatory molecules and cytokine-and chemokine-adjuvants. Although genetic vaccines have been significantly improved, they may not be sufficiently immunogenic for the therapeutic vaccination of patients with infectious diseases or cancer in clinical trials. One promising approach aimed at dramatically increasing the immunogenicity of genetic vaccines involves making them 'selfreplicating'. This can be accomplished by using a gene encoding RNA replicase, a polyprotein derived from alphaviruses, such as Sindbis virus. Replicase-containing RNA vectors are significantly more immunogenic than conventional plasmids, immunizing mice at doses as low as 0.1 μg of nucleic acid injected once intramuscularly. Cells transfected with 'self-replicating' vectors briefly produce large amounts of antigen before undergoing apoptotic death. This death is a likely result of requisite double-stranded (ds) RNA intermediates, which also have been shown to super-activate DC. Thus, the enhanced immunogenicity of 'self-replicating' genetic vaccines may be a result of the production of pro-inflammatory dsRNA, which mimics an RNA-virus infection of host cells.

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“…Thus, alternative explanations have been proposed for this phenomenon. These include the production of inhibitory factors released from infected T or B cells Fujinami et al, 1998), downregulation of cytokine receptors (Bell et al, 1997), the induction of apoptosis in both infected and uninfected cells (Esolen et al, 1995 ;Auwaerter et al, 1996) or downregulation of stimulatory factors such as IL-12 after cross-linking of the cognate MV receptor, CD46 (Karp et al, 1996). There is, however, also substantial evidence to suggest that a negative, cell contact-mediated signal is provided by infected cells directly that prevents mitogen-or T cell receptor-stimulated proliferation of uninfected lymphocytes (Sanchez-Lanier et al, 1988).…”

Section: Introductionmentioning

confidence: 99%

Measles virus-induced immunosuppression in vitro is associated with deregulation of G1 cell cycle control proteins.

Engelking

Fedorov

Lilischkis

et al. 1999

Journal of General Virology

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Virus-induced immunosuppression is the major cause of the high morbidity/mortality rates associated with acute measles. It has been shown previously that mitogen-dependent proliferation of peripheral blood lymphocytes (PBL) was strongly impaired after contact with the measles virus (MV) glycoproteins F and H expressed on the surface of infected cells, cells transfected with the corresponding expression constructs or UV-inactivated MV (UV-MV). The state of unresponsiveness was not associated with the induction of apoptosis, and a significant proportion of PBL was found to be arrested in the G 0 /G 1 phase of the cell cycle. It is now shown that cell cycle cessation, rather than complete arrest, is induced after MV glycoprotein contact. No obvious role was found for p53 in the induction of this unresponsiveness. With UV-MV as effector, downregulation of p27, an inhibitor of cyclin-dependent kinase (CDK)-cyclin complexes, was significantly delayed after mitogenic stimulation of human PBL. The activities of both CDK4/6-cyclin D and CDK2-cyclin E complexes for phosphorylation of exogenous substrates in vitro were strongly reduced. CDK4, CDK6, cyclins D3 and E and, to a minor extent, CDK2 failed to accumulate at the protein level after mitogenic stimulation in the presence of UV-MV. These data indicate that MV-induced proliferative unresponsiveness of PBL to mitogenic stimulation is associated with a drastic deregulation of the expression of cell cycle genes essential for the G 1 /S phase transition.

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Measles Virus Infection of Human T Cells Modulates Cytokine Generation and IL-2 Receptor Alpha Chain Expression

Cited by 20 publications

References 15 publications

Immune Containment and Consequences of Measles Virus Infection in Healthy and Immunocompromised Individuals

Immune Containment and Consequences of Measles Virus Infection in Healthy and Immunocompromised Individuals

DNA and RNA-based vaccines: principles, progress and prospects

Measles virus-induced immunosuppression in vitro is associated with deregulation of G1 cell cycle control proteins.

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