MOLECULAR MIMICRY AND POST-INFECTIOUS AUTOIMMUNITY: PATHOPHYSIOLOGICAL MECHANISMS OF AUTOIMMUNE ENCEPHALITIS MANIFESTATION FOLLOWING VIRAL INFECTIONS

Abstract

Autoimmune encephalitis (AIE) has emerged as one of the most clinically significant discoveries in contemporary neuroimmunology, reshaping the differential diagnosis of patients presenting with subacute psychiatric symptoms, seizures, and cognitive decline. A growing body of evidence links the onset of several forms of AIE, most notably anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis, to a preceding viral infection of the central nervous system, particularly herpes simplex virus type 1 (HSV-1) encephalitis. This article reviews the pathophysiological mechanisms by which viral infections can precipitate autoimmune neurological disease, with particular emphasis on molecular mimicry as a mechanistic framework, alongside complementary processes such as bystander activation, epitope spreading, and virus-induced blood-brain barrier disruption. The post-herpetic anti-NMDAR encephalitis model is examined as the paradigmatic example of post-infectious autoimmune encephalitis, illustrating how neuronal antigens released during viral cytolysis can become targets of a maladaptive humoral immune response. Understanding these mechanisms carries direct clinical relevance, as recognizing the temporal relationship between viral encephalitis and subsequent neurological relapse can guide earlier immunotherapy and improve patient outcomes.