Association of HLA-DRB1 and TNF genotypes with dengue hemorrhagic fever

Alagarasu, Kalichamy; Mulay, A.P.; Singh, Rupa; Gavade, V.; Shah, P.S.; Cecilia, D.

doi:10.1016/j.humimm.2013.01.027

Cited by 32 publications

(9 citation statements)

References 40 publications

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“…Our recent studies have shown that the association of human leukocyte antigen alleles with clinical outcomes of DENV infection is different from that of studies from other regions [21,22]. The virus populations circulating in India are also different from those in South East Asia [23].…”

Section: Introductionmentioning

confidence: 65%

Higher levels of dengue-virus-specific IgG and IgA during pre-defervescence associated with primary dengue hemorrhagic fever

et al. 2015

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Dengue hemorrhagic fever (DHF), although predominantly associated with secondary infections, has also been reported in primary infections. An enhanced immune response including antibodies and cytokines is implicated in the pathogenesis of secondary DHF. However, the factors operating in primary DHF are poorly understood. To understand the role of the antibody response, the relative levels of different antibody isotypes during the acute phase of infection in primary and secondary dengue infections were determined. Levels of DENV-specific IgM, IgG, IgA and IgE were measured in the serum samples of 200 dengue patients and 20 dengue-naïve individuals. Samples were collected within 15 days of onset of illness. The DENV-specific IgM levels were significantly higher in DF cases compared to DHF, which was more evident in secondary infections and in post-defervescence samples. The levels of IgG, IgA and IgE were higher in DHF cases, with greater significance in primary infections. A higher level of IgG in DHF cases was evident in pre-defervescence samples, whilst the IgE level was higher in pre- and post-defervescence samples. There was a significant correlation of IgG titres with platelet counts, with higher titres associated with lower platelet counts. It is speculated that IgG, IgA and IgE produced in response to primary infections may contribute to pathogenesis, whilst IgM produced in response to secondary infections may protect against progression to severe disease.

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Section: Introductionmentioning

confidence: 65%

Higher levels of dengue-virus-specific IgG and IgA during pre-defervescence associated with primary dengue hemorrhagic fever

et al. 2015

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“…Case fatality rates vary across populations and average about 5%. Many factors contribute to the risk for severe disease, including whether the patient has been previously infected by another serotype (Halstead et al 1970; Kurane et al 1991; Green & Rothman 2006; Midgley et al 2011; Rothman 2011), the genetic background of the individual (Sierra et al 2007; García et al 2011; Khor et al 2011; Alagarasu et al 2013), and the genetic makeup of the virus (Rosen 1977; Gubler et al 1978; Gubler et al 1981; Gubler 1988; Rico-Hesse et al 1997; Gubler 1998; Leitmeyer et al 1999). Control of dengue remains problematic, relying on vector control since there are as yet no vaccines available.…”

Section: Introductionmentioning

confidence: 99%

Insights into the molecular evolution of Dengue virus type 4 in Puerto Rico over two decades of emergence

Martin

Chirivella

et al. 2016

Virus Research

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Dengue has emerged globally as a major human health problem since the 1950s and is now the most important arboviral disease of humans, infecting nearly 400 million people annually. While some cases are asymptomatic, others can develop a febrile illness (dengue fever) or even progress to severe and fatal dengue. Dengue is caused by any of four closely related but distinct viruses, known as Dengue virus serotype 1 to 4 (DENV-1 to DENV-4) which are maintained in endemic transmission to humans in large urban centers of the tropics by Aedes mosquitoes. Since the early 1960s, Puerto Rico, a major metropolitan center in the Caribbean, has experienced increasingly larger and clinically more severe epidemics following the introduction of all four dengue serotypes. The first dengue hemorrhagic fever epidemic in 1986, and a particularly severe outbreak in 1998 were dominated by novel DENV-4 strains that evolved in Puerto Rico, replacing earlier strains and spreading throughout the region. Sequence characterization of 54 complete DENV-4 genomes and their comparative evolution against 74 previously published viral sequences from the region over several decades shows that DENV-4 strains from these periods were genetically distinct based on unique changes in the envelope and non-structural genes. Their replacement of earlier strains in Puerto Rico progressed rapidly, suggesting that strong natural selection played a role in their fixation. This study confirms that DENVs evolve through rapid lineage turnover driven in part by natural selection and genetic drift.

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“…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%

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.

249

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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Association of HLA-DRB1 and TNF genotypes with dengue hemorrhagic fever

Cited by 32 publications

References 40 publications

Higher levels of dengue-virus-specific IgG and IgA during pre-defervescence associated with primary dengue hemorrhagic fever

Higher levels of dengue-virus-specific IgG and IgA during pre-defervescence associated with primary dengue hemorrhagic fever

Insights into the molecular evolution of Dengue virus type 4 in Puerto Rico over two decades of emergence

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

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Association of HLA-DRB1 and TNF genotypes with dengue hemorrhagic fever

Cited by 32 publications

References 40 publications

Higher levels of dengue-virus-specific IgG and IgA during pre-defervescence associated with primary dengue hemorrhagic fever

Higher levels of dengue-virus-specific IgG and IgA during pre-defervescence associated with primary dengue hemorrhagic fever

Insights into the molecular evolution of Dengue virus type 4 in Puerto Rico over two decades of emergence

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

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