HLA-A, -B, -C, and -DRB1 allele frequencies in Cuban individuals with antecedents of dengue 2 disease: Advantages of the Cuban population for HLA studies of dengue virus infection

Sierra, Beatríz; Alegre, Roberto; Pérez, Ana B.; Garcı́a, Gissel; Sturn-Ramirez, Katharina; Obasanjo, Olugbenga O.; Aguirre, Eglys; Álvarez, Mayling; Rodríguez-Roche, Rosmari; Valdés, Luís; Kanki, Phyllis J.; Guzmán, María G.

doi:10.1016/j.humimm.2007.03.001

Cited by 96 publications

(72 citation statements)

References 59 publications

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“…These two alleles were selected because they are associated with increased resistance (DRB1*0401) or susceptibility (DRB1*0802) to severe DENV clinical outcomes (9,15,22) In the case of the DRB1*04-protective allele and secondary infections, responses were most vigorous and associated with the CD45RA + subset, thus resembling the pattern observed in the DRB1*07 responses ( Fig. 1 D and E).…”

Section: Significancementioning

confidence: 89%

“…Relatedly, a role for T cells in control of disease has been suggested by several studies that correlate the expression of certain HLA molecules with susceptibility to or protection from DENV disease (9)(10)(11)(12)(13)(14)(15). HLA molecules are one of the most polymorphic host factors in humans, with several thousand variants thus far known (16,17).…”

mentioning

confidence: 99%

“…For HLA class I MHC restricted responses, it has been recently shown that different allelic variants are associated with differential magnitude of anti-DENV responses and that HLA alleles known to be associated with increased risk of severe DENV disease are associated with weaker CD8 + T-cell responses (18). Similarly, certain MHC class II alleles have been described as associated with increased protection from severe disease (9,15,(19)(20)(21). Thus, T-cell responses are likely to contribute to protection from dengue disease.…”

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confidence: 99%

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Dengue virus infection elicits highly polarized CX3CR1⁺cytotoxic CD4⁺T cells associated with protective immunity

Weiskopf

Bangs

Sidney

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

266

300

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Dengue virus (DENV) is a rapidly spreading pathogen with unusual pathogenesis, and correlates of protection from severe dengue disease and vaccine efficacy have not yet been established. Although DENV-specific CD8 + T-cell responses have been extensively studied, the breadth and specificity of CD4 + T-cell responses remains to be defined. Here we define HLA-restricted CD4 + T-cell epitopes resulting from natural infection with dengue virus in a hyperepidemic setting. Ex vivo flow-cytometric analysis of DENVspecific CD4+ T cells revealed that the virus-specific cells were highly polarized, with a strong bias toward a CX3CR1 A ll four of the dengue virus serotypes (DENV 1-4) have spread rapidly within countries and across regions in the past few decades, resulting in an increased frequency of epidemics and severe dengue disease. Multiple serotypes circulate simultaneously in many tropical countries, and recent outbreaks have been reported in Europe and the continental United States (1, 2). These circumstances make dengue the most prevalent and rapidly spreading mosquito-borne viral disease in humans (3). Recent reports estimate that 390 million infections occur each year, with ∼25% of cases resulting in symptomatic disease (2).All four dengue serotypes can cause a spectrum of disease, ranging from self-limiting dengue fever to potentially lethal severe dengue disease, such as states of dengue hemorrhagic fever and Dengue shock syndrome, which are associated with the plasma leakage syndromes leading to visceral organ injury (4). It is not yet fully understood why only a subset of people infected with DENV progresses to severe disease. One risk factor for severe disease is the acquisition of DENV-reactive Abs before secondary infection with a different serotype (heterologous infection). These Abs can either be acquired from a previous infection with a different serotype or, in the case of infants, acquired from an immune mother (5, 6). It has been shown that subneutralizing levels of DENV-specific Abs exacerbate disease in a phenomenon termed Ab-dependent enhancement of infection (7,8). In brief, dengue-specific crossreactive Abs produced after an initial DENV infection combine with those produced after a second viral infection to form immune complexes that perpetuate infection by increasing the number of infected cells and, therefore, viral output per cell (6).The observation that only a minority of patients develops severe disease suggests that host genetic factors may play an important role in disease severity. Relatedly, a role for T cells in control of disease has been suggested by several studies that correlate the expression of certain HLA molecules with susceptibility to or protection from DENV disease (9-15). HLA molecules are one of the most polymorphic host factors in humans, with several thousand variants thus far known (16,17). Each HLA variant is present with variable frequency, depending on ethnic lineage and geographic locality. For HLA class I MHC restricted responses, it has been recently shown tha...

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Section: Significancementioning

confidence: 89%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Dengue virus infection elicits highly polarized CX3CR1⁺cytotoxic CD4⁺T cells associated with protective immunity

Weiskopf

Bangs

Sidney

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

266

300

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“…A role for T cells in control of DENV infection is suggested by several studies that implicate HLA associations as a genetic component to variable susceptibility to DENV disease (20)(21)(22)(23)(24)(25)(26). However, it has not been addressed whether these associations might indicate a positive or detrimental role for T-cell responses.…”

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confidence: 99%

Comprehensive analysis of dengue virus-specific responses supports an HLA-linked protective role for CD8 ⁺ T cells

Weiskopf

Angelo

Azeredo

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

533

645

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The role of CD8 + T cells in dengue virus infection and subsequent disease manifestations is not fully understood. According to the original antigenic sin theory, skewing of T-cell responses induced by primary infection with one serotype causes less effective response upon secondary infection with a different serotype, predisposing individuals to severe disease. A comprehensive analysis of CD8 + responses in the general population from the Sri Lankan hyperendemic area, involving the measurement of ex vivo IFNγ responses associated with more than 400 epitopes, challenges the original antigenic sin theory. Although skewing of responses toward primary infecting viruses was detected, this was not associated with impairment of responses either qualitatively or quantitatively. Furthermore, we demonstrate higher magnitude and more polyfunctional responses for HLA alleles associated with decreased susceptibility to severe disease, suggesting that a vigorous response by multifunctional CD8 + T cells is associated with protection from dengue virus disease.

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“…About 2.5% of those affected die. 152 Several studies [155][156][157][158][159][160][161][162][163] have been conducted about the role of HLA alleles or non HLA alleles in determining resistance, susceptibility or the severity of dengue viral infection, yet only superficial efforts have been made. Thus, a need for detailed genetic studies in different ethnic groups in different countries on a large number of patients is required.…”

Section: Hla and Dengue Virus Infectionmentioning

confidence: 99%

Major histocompatibility complex and its importance towards controlling infection

Longjam

Das

2017

Asian J Med Sci

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It is well documented that infectious pathogen burden and infected cell mass determine the clinical severity of infectious diseases, however, the ability of the host to recognize and process antigens to produce antibodies or the cellular immune response during infection could be under genetic control. The Major Histocompatibility Complex (MHC) or Human Leukocyte Antigen (HLA) system is the most intensively studied of all genetic systems because of its influence to many important traits, including resistance to infectious diseases, autoimmunity and immunological self or nonself compatibility. This is understandable in the light of the evolutionary pressure so that we are equipped to face the multitude of infectious challenges. Infectious diseases are a major selective pressure;and genes involved in the immune response are the most numerous and diverse in the human genome; reflecting the evolutionary advantages of a diverse immunological response to a wide range of infectious pathogens.Asian Journal of Medical Sciences Vol.8(2) 2017 1-13

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HLA-A, -B, -C, and -DRB1 allele frequencies in Cuban individuals with antecedents of dengue 2 disease: Advantages of the Cuban population for HLA studies of dengue virus infection

Cited by 96 publications

References 59 publications

Dengue virus infection elicits highly polarized CX3CR1⁺cytotoxic CD4⁺T cells associated with protective immunity

Dengue virus infection elicits highly polarized CX3CR1⁺cytotoxic CD4⁺T cells associated with protective immunity

Comprehensive analysis of dengue virus-specific responses supports an HLA-linked protective role for CD8 ⁺ T cells

Major histocompatibility complex and its importance towards controlling infection

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HLA-A, -B, -C, and -DRB1 allele frequencies in Cuban individuals with antecedents of dengue 2 disease: Advantages of the Cuban population for HLA studies of dengue virus infection

Cited by 96 publications

References 59 publications

Dengue virus infection elicits highly polarized CX3CR1+cytotoxic CD4+T cells associated with protective immunity

Dengue virus infection elicits highly polarized CX3CR1+cytotoxic CD4+T cells associated with protective immunity

Comprehensive analysis of dengue virus-specific responses supports an HLA-linked protective role for CD8 + T cells

Major histocompatibility complex and its importance towards controlling infection

Contact Info

Product

Resources

About

Dengue virus infection elicits highly polarized CX3CR1⁺cytotoxic CD4⁺T cells associated with protective immunity

Dengue virus infection elicits highly polarized CX3CR1⁺cytotoxic CD4⁺T cells associated with protective immunity

Comprehensive analysis of dengue virus-specific responses supports an HLA-linked protective role for CD8 ⁺ T cells