Elucidation of Nipah virus pathogenesis in the guinea pig by means of molecular, immunohistochemical, and in situ hybridization methodologies
Torres Velez, Fernando Javier
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Nipah virus (NiV) is a zoonotic disease that emerged in Southeast Asia at the beginning of this decade. Humans infected with NiV suffer from lethal febrile encephalitis and multisystemic vasculitis. In recent years, marked pulmonary involvement has characterized resent outbreaks in neighboring countries. The lack of effective therapeutics for prevention of the disease and the wide range distribution of the natural reservoir, the pteropid bat, makes its eradication unlikely and future outbreaks probable. In order to develop effective therapeutic modalities against NiV and possibly other henipaviruses, it is essential to understand how NiV causes disease in humans, or pathogenesis. This study was performed in order to find a suitable animal system to mimic the human disease process and further use this animal to elucidate key components of the disease pathogenesis. During the initial phase of this study NiV infection was successfully replicated in the guinea pigs. Key features of the human pathology were observed and characterized in this animal. During the second phase of the study, the guinea pig was used to evaluate the ability of NiV to induce or suppress apoptosis, as it has been shown in other Paramyxoviruses. Apoptotic cells were identified by means of an immunohistochemical (IHC) assay for active caspase 3 and Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. The data presented here, shows that NiV is able to suppress the apoptosis cascade in lymphoid organs early in the infection. Lymphoid organs such as the spleen and lymph nodes are major replication organs for NiV. In addition, the virus appears to induce apoptosis in organs where it can be shed into the environment, the urinary bladder and the uterus. The last phase of this investigation focused in characterizing the expression of cytokines of the early and adaptive immune response; tumor necrosis factor alpha (TNF-α), interleukin 1 (IL-1), and interferon gamma (IFN-γ). Localization of these cytokines was successful in control tissues but not in NiV infected guinea pig. This was likely the deleterious effects of the fixation and processing protocols employed for BSL-4 agents. However, viral influence cannot be discarded.