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Serum Proteomic characterization in Stump-tailed macaque (Macaca arctoides) with neutralizing antibodies against Dengue virus in Thailand

ABSTRACT: The dengue virus (DENV) is a leading public health problem world wide which transmitted by mosquito in the genus Ades. DENV is a single positive-stranded RNA virus with four serotypes, including DENV1-4. Infection with each serotype may provide lifelong immunity. However, reinfection with different serotypes promotes more severe disease symptoms from antibody-dependent enhancement (ADE). DENV causes a wide spectrum of clinical manifestations in humans including asymptomatic or mild dengue fever (DF), life-threatening dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). In Southeast Asia, the increasing transmission of zoonotic diseases from animals to humans, particularly in non-human primates (NHPs), presents a significant and concerning trend. NHPs play an important role as a reservoirs of DENV transmission. In our study, the serum of wild macaques with and without neutralizing antibodies against DENV was separated to profile the proteome using proteomics and bioinformatics techniques.

ORGANISM(S): Cellular Organisms

SUBMITTER: Wirasak Fungfuang

PROVIDER: PXD052111 | JPOST Repository | Thu May 08 00:00:00 BST 2025

REPOSITORIES: jPOST

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Project description:Occasional transmission of highly pathogenic avian H5N1 influenza viruses to humans causes severe pneumonia with high mortality. To better understand the mechanisms via which H5N1 viruses induce severe disease in humans, we infected cynomolgus macaques with six different H5N1 strains isolated from human patients and compared their pathogenicity and the global host responses to the virus infection. Although all H5N1 viruses replicated in the respiratory tract, there was substantial heterogeneity in their replicative ability and in the disease severity induced, which ranged from asymptomatic to fatal. A comparison of global gene expression between severe and mild disease cases indicated that interferon-induced up-regulation of genes related to innate immunity, apoptosis, and antigen processing/presentation in the early phase of infection was limited in severe disease cases, although interferon expression was up-regulated in both severe and mild cases. Furthermore, co-expression analysis of microarray data, which reveals the dynamics of host responses during the infection, demonstrated that the limited expression of these genes early in infection led to a failure to suppress virus replication and to the hyperinduction of genes related to immunity, inflammation, coagulation, and homeostasis in the late phase of infection, resulting in a more severe disease. Our data suggest that the attenuated interferon-induced activation of innate immunity, apoptosis, and antigen presentation in the early phase of H5N1 virus infection leads to subsequent severe disease outcome. Bronchial brushes for microarray studies were obtained from female cynomolgus macaques infected with influenza viruses. Three animals per group were inoculated with one of three H5N1 influenza viruses (VN3028II, VN30259 or VN3040). The early phase of infection refers to timepoints Pre (prior to infection), 1, and 3 days post-infection. The late phase of infection refers to days 5 and 7 post-infection. Samples collected prior to infection (labeled as Pre) served as control data for each infection group.

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Dataset Information

Serum Proteomic characterization in Stump-tailed macaque (Macaca arctoides) with neutralizing antibodies against Dengue virus in Thailand

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