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Comparative evaluation of permissiveness to dengue virus serotype 2 infection in primary rodent macrophages.

ABSTRACT: Infection with dengue virus presents a broad clinical spectrum, which can range from asymptomatic cases to severe cases that are characterised by haemorrhagic syndrome and/or shock. The reason for such variability remains unknown. This work evaluated the in vitro permissiveness of mouse, rat, hamster and guinea pig macrophages to infection by dengue virus 2 (DENV2). The results established that macrophages derived from the BALB/c mouse strain showed higher permissiveness to DENV2 infection than macrophages from other rodent species, although all rodent species studied had the C820T mutation in the oligoadenylate synthetase 1b gene, indicating no relationship to the different in vitro susceptibilities of mouse cells at this locus. Other molecular mechanisms related to flavivirus susceptibility remain to be explored.

SUBMITTER: Prada-Arismendy J

PROVIDER: S-EPMC3317054 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Comparative evaluation of permissiveness to dengue virus serotype 2 infection in primary rodent macrophages.

Prada-Arismendy Jeanette J Rincón Verónica V Castellanos Jaime E JE

Journal of tropical medicine 20120308

Infection with dengue virus presents a broad clinical spectrum, which can range from asymptomatic cases to severe cases that are characterised by haemorrhagic syndrome and/or shock. The reason for such variability remains unknown. This work evaluated the in vitro permissiveness of mouse, rat, hamster and guinea pig macrophages to infection by dengue virus 2 (DENV2). The results established that macrophages derived from the BALB/c mouse strain showed higher permissiveness to DENV2 infection than ...[more]

PMID: 22529871

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Project description:Dengue virus (DENV) is the causative agent of dengue fever (DF). This disease can be caused by any of four DENV serotypes (DENV1 to -4) which share 67 to 75% sequence homology with one another. The effect of subsequent infections with different serotypes on the T cell repertoire is not fully understood. We utilized mice transgenic for human leukocyte antigens (HLA) lacking the alpha/beta interferon (IFN-?/?) receptor to study responses to heterologous DENV infection. First, we defined the primary T cell response to DENV3 in the context of a wide range of HLA molecules. The primary DENV3 immune response recognized epitopes derived from all 10 DENV proteins, with a significant fraction of the response specific for structural proteins. This is in contrast to primary DENV2 infection, in which structural proteins are a minor component of the response, suggesting differential antigen immunodominance as a function of the infecting serotype. We next investigated the effect of secondary heterologous DENV infection on the T cell repertoire. In the case of both DENV2/3 and DENV3/2 heterologous infections, recognition of conserved/cross-reactive epitopes was either constant or expanded compared to that in homologous infection. Furthermore, in heterologous infection, previous infection with a different serotype impaired the development of responses directed to serotype-specific but not conserved epitopes. Thus, a detrimental effect of previous heterotypic responses might not be due to dysfunctional and weakly cross-reactive epitopes dominating the response. Rather, responses to the original serotype might limit the magnitude of responses directed against epitopes that are either cross-reactive to or specific for the most recently infecting serotype.DENV transmission occurs in more than 100 countries and is an increasing public health problem in tropical and subtropical regions. At present, no effective antiviral therapy or licensed vaccine exists, and treatment is largely supportive in nature. Disease can be caused by any of the four DENV serotypes (DENV1 to -4), which share a high degree of sequence homology with one another. In this study, we have addressed the question of how the T cell repertoire changes as a function of infections with different serotypes and of subsequent heterologous secondary infections. This is of particular interest in the field of dengue viruses, in which secondary infections with different DENV serotypes increase the risk of severe disease. Our results on the evolution of the immune response after primary and secondary infections provide new insights into HLA-restricted T cell responses against DENV relevant for the design of a vaccine against DENV.

Dataset Information

Comparative evaluation of permissiveness to dengue virus serotype 2 infection in primary rodent macrophages.

Publications

Comparative evaluation of permissiveness to dengue virus serotype 2 infection in primary rodent macrophages.

Similar Datasets

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