scholarly journals Hierarchical and Redundant Lymphocyte Subset Control Precludes Cytomegalovirus Replication during Latent Infection

1998 ◽  
Vol 188 (6) ◽  
pp. 1047-1054 ◽  
Author(s):  
Bojan Polić ◽  
Hartmut Hengel ◽  
Astrid Krmpotić ◽  
Joanne Trgovcich ◽  
Ivica Pavić ◽  
...  

Reactivation from latent cytomegalovirus (CMV) infection is often associated with conditions of immunosuppression and can result in fatal disease. Whether the maintenance of systemic CMV latency is mainly governed by factors of the infected cell or by immune control functions is unknown. Likewise, the putative immune control mechanisms which could prevent the induction and spread of recurrent CMV infection are not clearly identified. We took advantage of latently infected B cell–deficient mice and a sensitive method for virus detection to study CMV reactivation after ablation of lymphocyte subsets. A crucial role of both T lymphocytes and natural killer (NK) cells was demonstrated. Within 5 d after depletion of lymphocytes, productive infection occurred in 50% of mice, and 14 d later 100% of mice exhibited recurrent infection. A hierarchy of immune control functions of CD8+, NK, and CD4+ cells was established. Reactivation was rare if only one of the lymphocyte subsets was depleted, but was evident after removal of a further subset, indicating a functional redundancy of control mechanisms. The salivary glands were identified as the site of most rapid virus shedding, followed by the detection of recurrent virus in the lungs, and eventually in the spleen. Our findings document a previously unknown propensity of latent CMV genomes to enter productive infection immediately and with a high frequency after immune cell depletion. The data indicate that only the sustained cellular immune control prevents CMV replication and restricts the viral genome to a systemic state of latency.

2020 ◽  
Vol 13 (7) ◽  
pp. 1288-1293
Author(s):  
Obianuju Nkiruka Okoroafor ◽  
Paul Chukwuemeka Animoke ◽  
Edmund Chidiebere Mbegbu ◽  
Chinwe Justina Aronu ◽  
John Anelom Nwanta ◽  
...  

Background and Aim: Newcastle disease (ND) virus of free-range turkeys may be linked to outbreaks of ND in backyard chickens seen during Harmattan in Enugu State in Southeast Nigeria. This study aimed to determine the prevalence of ND virus and (NDV) detect NDV in the feces of free-range, domestic turkeys in Enugu, Nigeria. Materials and Methods: A total of 569 serum and 569 cloacal swab samples were collected from adult turkeys in selected households that keep turkeys and chickens together in the study area. The serum samples were assayed for antibodies against NDV using the hemagglutination inhibition (HI) test, whereas the cloacal samples were subjected to virus detection using a hemagglutination (HA) test. Results: A total of 186 serum samples (32.7%) were positive for NDV and 383 (67.3%) were negative. Of the 186 NDV-positive serum samples, 138 (74.2%) had HI titers ≥ 8. The remaining 48 (25.8%) serum samples had HI titers <8. NDV was detected from the cloacal swabs of turkeys with NDV -positive serum samples. Conclusion: The turkeys in this study were not previously vaccinated with the NDV vaccine; thus, those with NDV -positive serum samples and virus shedding in their feces may be potential risks to chickens reared in the same households as well as on commercial farms in the area. Those turkeys with sera negative for NDV are regarded to be at risk if they encounter a virulent strain of NDV. Regular vaccination of turkeys against the NDV is advised, especially in backyard farms, where turkeys are reared together with chickens and other species of poultry.


2019 ◽  
Vol 3 (1) ◽  
pp. e000455
Author(s):  
Paulo Paixão ◽  
Maria João Brito ◽  
Daniel Virella ◽  
Maria Teresa Neto

ObjectiveHuman cytomegalovirus (CMV) is the most widespread agent of congenital infection in humans and is still a challenging issue. Despite lower rates of vertical transmission being associated with recurrent infection when compared with primary infection, the first still represents the majority of congenital infections worldwide. Based on data from active reporting, we explored the influence of maternal primary/non-primary infection both on the presentation and outcome of congenital CMV infection in early childhood.DesignInfants with positive viruria during the first 3 weeks of life were reported through the Portuguese Paediatric Surveillance Unit.PatientsInfants born between 2006 and 2011 with confirmed congenital CMV infection.MethodsMaternal infection was considered primary if CMV IgG seroconversion occurred during pregnancy or low avidity IgG was documented; it was considered non-primary if positive IgG was documented before pregnancy or high avidity CMV IgG was present early in pregnancy. Follow-up questionnaires were sent up to 6 years of age.ResultsForty confirmed cases of congenital CMV infection were reported (6.6:105 live births, 95% CI 4.81 to 8.92); 22 out of 40 were asymptomatic. The odds for non-primary maternal infection if the offspring was symptomatic at birth were 6.2 (95% CI 1.2 to 32.27).ConclusionThe reported number of confirmed cases of congenital CMV infection was much lower than expected. Under-reporting and missed diagnosis were considered possible reasons. Non-primary maternal infections were associated with symptomatic congenital CMV infection in the offspring. Maternal recurrent infections can have a significant impact on the total number of symptomatic infections in Portugal.


2015 ◽  
Vol 100 (7) ◽  
pp. 667-672 ◽  
Author(s):  
Lizzy Rivers ◽  
H Bobby Gaspar

Severe combined immunodeficiency (SCID) is a rare but important condition. Affected infants are born with profound abnormalities of immune cell function that lead to severe and recurrent infection that are almost always fatal in the first year of life without treatment. Infants with SCID are often initially seen by general paediatricians in the hospital care setting, and the recognition of the cardinal features of the disease and alertness to specific laboratory parameters are important in making an early diagnosis. There is also increasing interest in newborn screening for SCID, which has the potential to significantly improve outcome through early diagnosis and implementation of prophylactic medications. Definitive treatments such as haematopoietic stem cell transplantation and gene therapy have also made major advances over the last decade and again promise to improve the overall outcome for SCID with reduced long-term toxicities. In this review, we highlight some of the major advances in diagnosis and management of the disease, but we also want to emphasise the important role of the general paediatrician in making an early diagnosis and in ongoing management.


2009 ◽  
Vol 83 (19) ◽  
pp. 10293-10298 ◽  
Author(s):  
Verena Böhm ◽  
Christof K. Seckert ◽  
Christian O. Simon ◽  
Doris Thomas ◽  
Angélique Renzaho ◽  
...  

ABSTRACT CD8 T cells control cytomegalovirus (CMV) infection in bone marrow transplantation recipients and persist in latently infected lungs as effector memory cells for continuous sensing of reactivated viral gene expression. Here we have addressed the question of whether viral immunoevasins, glycoproteins that specifically interfere with antigen presentation to CD8 T cells, have an impact on viral latency in the murine model. The data show that deletion of immunoevasin genes in murine CMV accelerates the clearance of productive infection during hematopoietic reconstitution and leads to a reduced latent viral genome load, reduced latency-associated viral transcription, and a lower incidence of recurrence in lung explants.


EBioMedicine ◽  
2018 ◽  
Vol 27 ◽  
pp. 40-50 ◽  
Author(s):  
Wang Zhang ◽  
Anoop T. Ambikan ◽  
Maike Sperk ◽  
Robert van Domselaar ◽  
Piotr Nowak ◽  
...  

Hepatology ◽  
2015 ◽  
Vol 62 (3) ◽  
pp. 915-931 ◽  
Author(s):  
Miwa Morita ◽  
Daniel Joyce ◽  
Charles Miller ◽  
John J. Fung ◽  
Lina Lu ◽  
...  

Author(s):  
Alpana Waghmare ◽  
Elizabeth M. Krantz ◽  
Subhasish Baral ◽  
Emma Vasquez ◽  
Tillie Loeffelholz ◽  
...  

AbstractThe SARS-CoV-2 pandemic demonstrates the need for accurate and convenient approaches to diagnose and therapeutically monitor respiratory viral infections. We demonstrated that self-sampling with foam swabs is well-tolerated and provides quantitative viral output concordant with flocked swabs. Using longitudinal home-based self-sampling, we demonstrate nasal cytokine levels correlate and cluster according to immune cell of origin. Periods of stable viral loads are followed by rapid elimination, which could be coupled with cytokine expansion and contraction using mathematical models. Nasal foam swab self-sampling at home provides a precise, mechanistic readout of respiratory virus shedding and local immune responses.


Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 766 ◽  
Author(s):  
John J. Heath ◽  
Michael D. Grant

Aging reflects long-term decline in physiological function and integrity. Changes arise at a variable pace governed by time-dependent and -independent mechanisms that are themselves complex, interdependent and variable. Molecular decay produces inferior cells that eventually dominate over healthy counterparts in tissues they comprise. In a form of biological entropy, progression from molecular through cellular to tissue level degeneration culminates in organ disease or dysfunction, affecting systemic health. To better understand time-independent contributors and their potential modulation, common biophysical bases for key molecular and cellular changes underlying age-related physiological deterioration must be delineated. This review addresses the potential contribution of cytomegalovirus (CMV)-driven T cell proliferation to cellular senescence and immunosenescence. We first describe molecular processes imposing cell cycle arrest, the foundation of cellular senescence, then focus on the unique distribution, phenotype and function of CMV-specific CD8+ T cells in the context of cellular senescence and “inflammaging”. Their features position CMV infection as a pathogenic accelerant of immune cell proliferation underlying immune senescence. In human immunodeficiency virus (HIV) infection, where increased inflammation and exaggerated anti-CMV immune responses accelerate immune senescence, CMV infection has emerged as a major factor in unhealthy aging. Thus, we speculate on mechanistic links between CMV-specific CD8+ T-cell expansion, immune senescence and prevalence of age-related disorders in HIV infection.


1999 ◽  
Vol 87 (3) ◽  
pp. 1178-1185 ◽  
Author(s):  
Shawn G. Rhind ◽  
Greg A. Gannon ◽  
Pang N. Shek ◽  
Ingrid K. M. Brenner ◽  
Yvonne Severs ◽  
...  

The contribution of hyperthermia to the differential leukocytosis of exercise remains obscure. This study examined changes in circulating sympathoadrenal hormone concentrations and patterns of leukocyte and lymphocyte subset (CD3+, CD4+, CD8+, CD19+, CD3−16+/56+) redistribution during exercise, with and without a significant rise of rectal temperature (Tre). Ten healthy men [age 26.9 ± 5.7 (SD) yr, body mass 76.0 ± 10.9 kg, body fat 13.9 ± 4.6%, peak O2consumption: 48.0 ± 12.4 ml ⋅ kg−1⋅ min−1] exercised for 40 min (65% peak O2consumption) during water immersion at 39 or 18°C. Treincreased from 37.2 to 39.3°C ( P < 0.0001) after 40 min of exercise in 39°C water but was held constant to an increment of 0.5°C during exercise in 18°C water. Application of this thermal clamp reduced exercise-associated increments of plasma epinephrine (Epi) and norepinephrine (NE) by >50% ( P < 0.05) and abolished the postexercise increase in cortisol. Thermal clamping also reduced the exercise-induced leukocytosis and lymphocytosis. Multiple regression demonstrated that Trehad no direct association with lymphocyte subset mobilization but was significantly ( P < 0.0001) correlated with hormone levels. Epi was an important determinant of total leukocytes, lymphocytes, and CD3+, CD4+, CD8+, and CD3−CD16+/56+subset redistribution. The relationship between NE and lymphocyte subsets was weaker than that with Epi, with the exception of CD3−CD16+/56+counts, which were positively ( P < 0.0001) related to NE. Cortisol was negatively associated with leukocytes, CD14+monocytes, and CD19+B- and CD4+T-cell subsets but was positively related to granulocytes. We conclude that hyperthermia mediates exercise-induced immune cell redistribution to the extent that it causes sympathoadrenal activation, with alterations in circulating Epi, NE, and cortisol.


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