NEUROPATHOGENESIS OF NIPAH VIRUS INFECTION: MOLECULAR NEUROINVASION, SYNAPTIC DYSFUNCTION, AND NEUROINFLAMMATORY CASCADES

Abstract

Nipah virus (NiV) is an emerging zoonotic pathogen of the genus Henipavirus that endangers human health with a high fatality rate, neurotropism, and a lack of approved therapeutics. The article is a critical review of the neuropathogenesis of NiV, which dwells on synaptic dysfunction, the integration of molecular neuroinvasion mechanisms, and neuroinflammatory cascades. NiV uses several routes of entry into the central nervous system (CNS), among which are endothelial infection with the breakage of the blood-brain barrier, transportation by leukocytes as a Trojan horse, and direct neuroproliferation through the olfactory tract. In the CNS, the virus is characterized by high neuronal tropism and, at the same time, causes endothelial damage and an immune response, which leads to a dual pathology of vasculopathy and parenchymal encephalitis. In addition to structural damage, there is emerging evidence that NiV-associated neurological disease is highly influenced by synaptic-level functional pathology comprising neuromodulator imbalance, calcium hyporegulation, and excitotoxicity, all of which impair the integrity of neural circuits. Such mechanisms offer a reasonable account of acute encephalitic expressions, as well as delayed and relapsing neurological syndromes. Although the biology of viruses has been studied, the current treatment methods are mainly supportive, and the antiviral and immunotherapeutic methods are still being tested. This review shows that there are some critical mechanistic gaps and that synaptic and neuroimmune pathways are currently under-explored but can be used as targets of therapeutic intervention in the future.