Abstract
Cytomegalovirus (CMV) is a beta-herpes virus present in a latent form in most people worldwide. In immunosuppressed individuals, CMV can reactivate and cause serious clinical complications, but the effect of the latent state on healthy people remains elusive. We undertook a systems approach to understand the differences between seropositive and negative subjects and measured hundreds of immune system components from blood samples including cytokines and chemokines, immune cell phenotyping, gene expression, ex vivo cell responses to cytokine stimuli and the antibody response to seasonal influenza vaccination. As expected, we found decreased responses to vaccination and an overall down-regulation of immune components in aged individuals regardless of CMV serostatus. In contrast, CMV-infected young adults exhibited an overall up-regulation of immune components including enhanced antibody responses to influenza vaccination, increased CD8+ T cell sensitivity, and elevated levels of circulating IFN-γ compared to uninfected individuals. Experiments with young mice infected with murine CMV also showed significant protection from an influenza virus challenge compared with uninfected animals, although this effect declined with time. These data show that CMV and its murine equivalent can have a beneficial effect on the immune response of young, healthy individuals, which may explain the continued coexistence of CMV and mammals throughout their evolution.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4505610/
Cytomegalovirus infection improves immune responses to influenza
The "silent" global burden of congenital cytomegalovirus.
Abstract
Human cytomegalovirus (CMV) is a leading cause of congenital infections worldwide. In the developed world, following the virtual elimination of circulating rubella, it is the commonest nongenetic cause of childhood hearing loss and an important cause of neurodevelopmental delay. The seroprevalence of CMV in adults and the incidence of congenital CMV infection are highest in developing countries (1 to 5% of births) and are most likely driven by nonprimary maternal infections. However, reliable estimates of prevalence and outcome from developing countries are not available. This is largely due to the dogma that maternal preexisting seroimmunity virtually eliminates the risk for sequelae. However, recent data demonstrating similar rates of sequelae, especially hearing loss, following primary and nonprimary maternal infection have underscored the importance of congenital CMV infection in resource-poor settings. Although a significant proportion of congenital CMV infections are attributable to maternal primary infection in well-resourced settings, the absence of specific interventions for seronegative mothers and uncertainty about fetal prognosis have discouraged routine maternal antibody screening. Despite these challenges, encouraging results from prototype vaccines have been reported, and the first randomized phase III trials of prenatal interventions and prolonged postnatal antiviral therapy are under way. Successful implementation of strategies to prevent or reduce the burden of congenital CMV infection will require heightened global awareness among clinicians and the general population. In this review, we highlight the global epidemiology of congenital CMV and the implications of growing knowledge in areas of prevention, diagnosis, prognosis, and management for both low (50 to 70%)- and high (>70%)-
https://www.ncbi.nlm.nih.gov/m/pubmed/23297260
Human cytomegalovirus (CMV) is a leading cause of congenital infections worldwide. In the developed world, following the virtual elimination of circulating rubella, it is the commonest nongenetic cause of childhood hearing loss and an important cause of neurodevelopmental delay. The seroprevalence of CMV in adults and the incidence of congenital CMV infection are highest in developing countries (1 to 5% of births) and are most likely driven by nonprimary maternal infections. However, reliable estimates of prevalence and outcome from developing countries are not available. This is largely due to the dogma that maternal preexisting seroimmunity virtually eliminates the risk for sequelae. However, recent data demonstrating similar rates of sequelae, especially hearing loss, following primary and nonprimary maternal infection have underscored the importance of congenital CMV infection in resource-poor settings. Although a significant proportion of congenital CMV infections are attributable to maternal primary infection in well-resourced settings, the absence of specific interventions for seronegative mothers and uncertainty about fetal prognosis have discouraged routine maternal antibody screening. Despite these challenges, encouraging results from prototype vaccines have been reported, and the first randomized phase III trials of prenatal interventions and prolonged postnatal antiviral therapy are under way. Successful implementation of strategies to prevent or reduce the burden of congenital CMV infection will require heightened global awareness among clinicians and the general population. In this review, we highlight the global epidemiology of congenital CMV and the implications of growing knowledge in areas of prevention, diagnosis, prognosis, and management for both low (50 to 70%)- and high (>70%)-
https://www.ncbi.nlm.nih.gov/m/pubmed/23297260
Debbie
Re: Cytomegalovirus infection improves immune responses to influenza
When was ASPS first documented , USA wise?
Memorial Sloan Kettering (MSK)
“Credit for the original description of ASPS traditionally goes to Christopherson, then a fellow in surgical pathology at Memorial Sloan Kettering Cancer Center. With the publication of a study of 12 cases in 1952, Christopherson et al. established the descriptive term "alveolar soft part sarcoma" for a unique soft-tissue tumor.1 This tumor was first defined histologically by the presence of cells arranged in nests ("alveoli") separated by delicate partitions of connective tissue containing sinusoidal vascular channels lined by flattened endothelium.1 Prior to Christopherson’s publication, the entity ASPS had been described by a variety of other names, including "malignant myoblastoma", "granular cell myoblastoma" and "malignant granular cell myoblastoma."2-6 While Christopherson et al. did not describe the intracytoplasmic crystalline structures that have become one of the hallmarks of ASPS, they did quote an unpublished letter from Dr. Pierre Masson, who noted the intracytoplasmic crystals.1 Therefore, credit for the intracytoplasmic crystals belongs to Dr. Masson, who later in 1956 published a study on the ultrastructural appearance of these structures.7Unknown to Christopherson and colleagues, ASPS had been described by Smetana and Scott one year earlier, as malignant tumors of non-chromaffin paraganglia.8They chose this term because the tumors resembled non-physiologically active paraganglia, postulating that primitive paraganglia-like structures may perhaps normally occur in the somatic soft tissues (this hypothesis was later discredited). Smetana and Scott also independently observed the intracytoplasmic crystals of ASPS, describing them as rod-shaped, coarse, basophilic bodies of unknown nature.8”
http://sarcomahelp.org/asps.html
Memorial Sloan Kettering (MSK)
“Credit for the original description of ASPS traditionally goes to Christopherson, then a fellow in surgical pathology at Memorial Sloan Kettering Cancer Center. With the publication of a study of 12 cases in 1952, Christopherson et al. established the descriptive term "alveolar soft part sarcoma" for a unique soft-tissue tumor.1 This tumor was first defined histologically by the presence of cells arranged in nests ("alveoli") separated by delicate partitions of connective tissue containing sinusoidal vascular channels lined by flattened endothelium.1 Prior to Christopherson’s publication, the entity ASPS had been described by a variety of other names, including "malignant myoblastoma", "granular cell myoblastoma" and "malignant granular cell myoblastoma."2-6 While Christopherson et al. did not describe the intracytoplasmic crystalline structures that have become one of the hallmarks of ASPS, they did quote an unpublished letter from Dr. Pierre Masson, who noted the intracytoplasmic crystals.1 Therefore, credit for the intracytoplasmic crystals belongs to Dr. Masson, who later in 1956 published a study on the ultrastructural appearance of these structures.7Unknown to Christopherson and colleagues, ASPS had been described by Smetana and Scott one year earlier, as malignant tumors of non-chromaffin paraganglia.8They chose this term because the tumors resembled non-physiologically active paraganglia, postulating that primitive paraganglia-like structures may perhaps normally occur in the somatic soft tissues (this hypothesis was later discredited). Smetana and Scott also independently observed the intracytoplasmic crystals of ASPS, describing them as rod-shaped, coarse, basophilic bodies of unknown nature.8”
http://sarcomahelp.org/asps.html
Debbie
History of the cytomegalovirus.
Abstract
Because it is capable of producing both congenital and infections, the cytomegalovirus (CMV) has become an extremely important pathogen, and review of its history is pertinent. Inclusion-bearing cells were first shown by Ribbert in 1881. Goodpasture and Talbert in 1921 were the first to suggest that the "cytomegalia" could be due to a viral agent. In 1950, Smith and Vellios showed that infection may occur in utero. The introduction of exfoliative cytology methods allowed identification of characteristic cells in the urine of infected infants. Smith in 1956, Rowe and coworkers in 1956, and Weller et al in 1957 independently isolated human CMV strains. In 1960, Weller and coworkers proposed the term "cytomegalovirus" and subsequently isolated CMV from the urine of infants with generalized disease. CMV has now become one of the most common opportunistic pathogens encountered in patients immunocompromised from congenital or acquired causes such as AIDS or transplantation procedures.
https://www.ncbi.nlm.nih.gov/m/pubmed/9042169/
Because it is capable of producing both congenital and infections, the cytomegalovirus (CMV) has become an extremely important pathogen, and review of its history is pertinent. Inclusion-bearing cells were first shown by Ribbert in 1881. Goodpasture and Talbert in 1921 were the first to suggest that the "cytomegalia" could be due to a viral agent. In 1950, Smith and Vellios showed that infection may occur in utero. The introduction of exfoliative cytology methods allowed identification of characteristic cells in the urine of infected infants. Smith in 1956, Rowe and coworkers in 1956, and Weller et al in 1957 independently isolated human CMV strains. In 1960, Weller and coworkers proposed the term "cytomegalovirus" and subsequently isolated CMV from the urine of infants with generalized disease. CMV has now become one of the most common opportunistic pathogens encountered in patients immunocompromised from congenital or acquired causes such as AIDS or transplantation procedures.
https://www.ncbi.nlm.nih.gov/m/pubmed/9042169/
Debbie
Severe Symptomatic Primary Human Cytomegalovirus Infection despite Effective Innate and Adaptive Immune Responses
ABSTRACT
Primary human cytomegalovirus (HCMV) infection usually goes unnoticed, causing mild or no symptoms in immunocompetent individuals. However, some rare severe clinical cases have been reported without investigation of host immune responses or viral virulence. In the present study, we investigate for the first time phenotypic and functional features, together with gene expression profiles in immunocompetent adults experiencing a severe primary HCMV infection. Twenty primary HCMV-infected patients (PHIP) were enrolled, as well as 26 HCMV-seronegative and 39 HCMV-seropositive healthy controls. PHIP had extensive lymphocytosis marked by massive expansion of natural killer (NK) and T cell compartments. Interestingly, PHIP mounted efficient innate and adaptive immune responses with a deep HCMV imprint, revealed mainly by the expansion of NKG2C+ NK cells, CD16+ Vδ2(−) γδ T cells, and conventional HCMV-specific CD8+ T cells. The main effector lymphocytes were activated and displayed an early immune phenotype that developed toward a more mature differentiated status. We suggest that both massive lymphocytosis and excessive lymphocyte activation could contribute to massive cytokine production, known to mediate tissue damage observed in PHIP. Taken together, these findings bring new insights into the comprehensive understanding of immune mechanisms involved during primary HCMV infection in immunocompetent individuals.
IMPORTANCE HCMV-specific immune responses have been extensively documented in immunocompromised patients and during in utero acquisition. While it usually goes unnoticed, some rare severe clinical cases of primary HCMV infection have been reported in immunocompetent patients. However, host immune responses or HCMV virulence in these patients has not so far been investigated. In the present study, we show massive expansion of NK and T cell compartments during the symptomatic stage of acute HCMV infection. The patients mounted efficient innate and adaptive immune responses with a deep HCMV imprint. The massive lymphocytosis could be the result of nonadapted or uncontrolled immune responses limiting the effectiveness of the specific responses mounted. Both massive lymphocytosis and excessive lymphocyte activation could contribute to massive cytokine production, known to mediate tissue damage. Furthermore, we cannot exclude a delayed immune response caused by immune escape established by HCMV strains.
KEYWORDS: HCMV, NK cells, T lymphocytes, adaptive immunity, innate immunity
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5309965/
Primary human cytomegalovirus (HCMV) infection usually goes unnoticed, causing mild or no symptoms in immunocompetent individuals. However, some rare severe clinical cases have been reported without investigation of host immune responses or viral virulence. In the present study, we investigate for the first time phenotypic and functional features, together with gene expression profiles in immunocompetent adults experiencing a severe primary HCMV infection. Twenty primary HCMV-infected patients (PHIP) were enrolled, as well as 26 HCMV-seronegative and 39 HCMV-seropositive healthy controls. PHIP had extensive lymphocytosis marked by massive expansion of natural killer (NK) and T cell compartments. Interestingly, PHIP mounted efficient innate and adaptive immune responses with a deep HCMV imprint, revealed mainly by the expansion of NKG2C+ NK cells, CD16+ Vδ2(−) γδ T cells, and conventional HCMV-specific CD8+ T cells. The main effector lymphocytes were activated and displayed an early immune phenotype that developed toward a more mature differentiated status. We suggest that both massive lymphocytosis and excessive lymphocyte activation could contribute to massive cytokine production, known to mediate tissue damage observed in PHIP. Taken together, these findings bring new insights into the comprehensive understanding of immune mechanisms involved during primary HCMV infection in immunocompetent individuals.
IMPORTANCE HCMV-specific immune responses have been extensively documented in immunocompromised patients and during in utero acquisition. While it usually goes unnoticed, some rare severe clinical cases of primary HCMV infection have been reported in immunocompetent patients. However, host immune responses or HCMV virulence in these patients has not so far been investigated. In the present study, we show massive expansion of NK and T cell compartments during the symptomatic stage of acute HCMV infection. The patients mounted efficient innate and adaptive immune responses with a deep HCMV imprint. The massive lymphocytosis could be the result of nonadapted or uncontrolled immune responses limiting the effectiveness of the specific responses mounted. Both massive lymphocytosis and excessive lymphocyte activation could contribute to massive cytokine production, known to mediate tissue damage. Furthermore, we cannot exclude a delayed immune response caused by immune escape established by HCMV strains.
KEYWORDS: HCMV, NK cells, T lymphocytes, adaptive immunity, innate immunity
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5309965/
Debbie
Vaccination against the human cytomegalovirus
Abstract
The human cytomegalovirus (HCMV) is the most important infectious cause of congenital abnormalities and also of infectious complications of transplantation. The biology of the infection is complex and acquired immunity does not always prevent reinfection. Nevertheless, vaccine development is far advanced, with numerous candidate vaccines being tested, both live and inactivated. This article summarizes the status of the candidate vaccines.
https://www.sciencedirect.com/science/a ... 0X18302883
The human cytomegalovirus (HCMV) is the most important infectious cause of congenital abnormalities and also of infectious complications of transplantation. The biology of the infection is complex and acquired immunity does not always prevent reinfection. Nevertheless, vaccine development is far advanced, with numerous candidate vaccines being tested, both live and inactivated. This article summarizes the status of the candidate vaccines.
https://www.sciencedirect.com/science/a ... 0X18302883
Debbie
Vaccination against the human cytomegalovirus
Introduction
The human cytomegalovirus, here abbreviated as CMV, is perhaps the most ubiquitous of human infections. Although better hygiene and lesser close contact between children and adults have decreased prevalence of CMV in developed countries, virtually 100% of adults in low- and middle-income countries have been infected when young. CMV infects T cells and modifies their responses. It is suspected in contributing to arteriosclerosis and immunosenescence and may promote cancers through an oncomoduleatory* effect. However, its principal medical importance is as the most common congenital infection throughout the world, causing most commonly hearing loss but also in some cases microcephaly, mental retardation, hepatosplenomegaly and thrombocytopenic purpura. As a generalization, between 1 in 200 and 1 in 30 newborns are infected by CMV transmitted from the mother. The seriousness of the infection in the fetus depends on whether the mother is seropositive or seronegative for CMV. Infections in seronegative pregnant women transmitted to the fetus carry the worst prognosis, but fetuses infected by seropositive mothers may also suffer serious consequences [1].
In addition, CMV is the most common infection complicating transplantation. Solid organ transplant patients who receive a transplant from a seropositive donor may suffer disease and seropositive hematogenous stem cell recipients may reactivate CMV due to immunosuppression [2], [3]. These infections may result in serious disease and rejection of the transplant.
In this article we review efforts to prevent CMV infections and their consequences in susceptible populations through immunization. Such efforts have been pursued for almost 50 years and today there is a wide range of candidate vaccines.
The human cytomegalovirus, here abbreviated as CMV, is perhaps the most ubiquitous of human infections. Although better hygiene and lesser close contact between children and adults have decreased prevalence of CMV in developed countries, virtually 100% of adults in low- and middle-income countries have been infected when young. CMV infects T cells and modifies their responses. It is suspected in contributing to arteriosclerosis and immunosenescence and may promote cancers through an oncomoduleatory* effect. However, its principal medical importance is as the most common congenital infection throughout the world, causing most commonly hearing loss but also in some cases microcephaly, mental retardation, hepatosplenomegaly and thrombocytopenic purpura. As a generalization, between 1 in 200 and 1 in 30 newborns are infected by CMV transmitted from the mother. The seriousness of the infection in the fetus depends on whether the mother is seropositive or seronegative for CMV. Infections in seronegative pregnant women transmitted to the fetus carry the worst prognosis, but fetuses infected by seropositive mothers may also suffer serious consequences [1].
In addition, CMV is the most common infection complicating transplantation. Solid organ transplant patients who receive a transplant from a seropositive donor may suffer disease and seropositive hematogenous stem cell recipients may reactivate CMV due to immunosuppression [2], [3]. These infections may result in serious disease and rejection of the transplant.
In this article we review efforts to prevent CMV infections and their consequences in susceptible populations through immunization. Such efforts have been pursued for almost 50 years and today there is a wide range of candidate vaccines.
Last edited by D.ap on Fri Feb 21, 2020 7:16 pm, edited 2 times in total.
Debbie
Re: Cytomegalovirus infection improves immune responses to influenza
*? oncomoduleatory?
A misprint ?
A misprint ?
Debbie