54 research outputs found
Identification and HLA-Tetramer-Validation of Human CD4(+) and CD8(+) T Cell Responses against HCMV Proteins IE1 and IE2
Human cytomegalovirus (HCMV) is an important human pathogen. It is a leading cause of congenital infection and a leading infectious threat to recipients of solid organ transplants as well as of allogeneic hematopoietic cell transplants. Moreover, it has recently been suggested that HCMV may promote tumor development. Both CD4+ and CD8+ T cell responses are important for long-term control of the virus, and adoptive transfer of HCMV-specific T cells has led to protection from reactivation and HCMV disease. Identification of HCMV-specific T cell epitopes has primarily focused on CD8+ T cell responses against the pp65 phosphoprotein. In this study, we have focused on CD4+ and CD8+ T cell responses against the immediate early 1 and 2 proteins (IE1 and IE2). Using overlapping peptides spanning the entire IE1 and IE2 sequences, peripheral blood mononuclear cells from 16 healthy, HLA-typed, donors were screened by ex vivo IFN-Îł ELISpot and in vitro intracellular cytokine secretion assays. The specificities of CD4+ and CD8+ T cell responses were identified and validated by HLA class II and I tetramers, respectively. Eighty-one CD4+ and 44 CD8+ T cell responses were identified representing at least seven different CD4 epitopes and 14 CD8 epitopes restricted by seven and 11 different HLA class II and I molecules, respectively, in total covering 91 and 98% of the Caucasian population, respectively. Presented in the context of several different HLA class II molecules, two epitope areas in IE1 and IE2 were recognized in about half of the analyzed donors. These data may be used to design a versatile anti-HCMV vaccine and/or immunotherapy strategy
Evolving uses of oral reverse transcriptase inhibitors in the HIV-1 epidemic: From treatment to prevention
The HIV epidemic continues unabated, with no highly effective vaccine and no cure. Each new infection has significant economic, social and human costs and prevention efforts are now as great a priority as global antiretroviral therapy (ART) scale up. Reverse transcriptase inhibitors, the first licensed class of ART, have been at the forefront of treatment and prevention of mother to child transmission over the past two decades. Now, their use in adult prevention is being
The "silent" global burden of congenital cytomegalovirus.
SUMMARY
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%)-seroprevalence settings
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