Multiple sclerosis is a demyelinating autoimmune disease of the central nervous system (CNS) that severely impairs the individuals motor and sensory functions. At present, its cause or causes are unknown, and the available treatments only decrease the frequency of inflammatory relapses but do not prevent chronic damage and neurologic decline. There is evidence that suggests that viruses may play roles in multiple sclerosis onset and pathogenesis by acting as environmental triggers. Importantly, viruses belonging to the Herpesviridae family, which are acquired at early stages of life, and cause lifelong infections have been defined as major candidates for triggering or exacerbating this disease. Currently, only a few studies have assessed a potential role for herpes simplex viruses in multiple sclerosis. Noteworthy, herpes simplex virus type 1 (HSV-1) DNA has been found in cerebrospinal fluid and peripheral blood of patients with multiple sclerosis relapses, as well as more frequently in post-mortem brain samples of individuals with multiple sclerosis than healthy controls. Notably, HSV-1 infections are mainly asymptomatic, and this virus may reach the brain throughout life without evident clinical symptoms. Moreover, accumulating data suggests that persistent HSV-1 infection in the brain could produce prolonged neuroinflammation due to continuous subclinical reactivations leading to neurodegenerative disorders in susceptible individuals. The goal of this thesis was to determine whether asymptomatic HSV-1 infection favors the onset of multiple sclerosis and its severity. We studied this question by using animals that recapitulate several aspects related to multiple sclerosis disease and HSV-1 infection in humans. First, we infected mice with a sublethal dose of HSV-1, waited for their recovery from acute infection at least 30 days, and then we induced experimental autoimmune encephalomyelitis (EAE), the main animal model used for studying multiple sclerosis disease. The onset and severity of multiple sclerosis symptoms in the EAE mouse model was compared with non-infected animals. We determined the populations of immune cells infiltrating the CNS of mice after HSV-1 infection and EAE induction, as well as cytokines produced in this tissue once autoimmunity was initiated. We also assessed the permeability of the blood-brain barrier (BBB) 30 days post-HSV-1 infection. Our results show that a previous infection with HSV-1 accelerates the onset of EAE and enhances disease severity. Moreover, the animals previously infected with HSV-1, and induced to develop EAE undergo increased CNS inflammation as compared to uninfected animals, which was characterized by prolongated microglia cell activation, an elevated infiltration of CD4+ T cells in the brain and increased infiltration of neutrophils in the spinal cord, as well as significant levels of IL-6 and IL-1? mRNA expression in these tissues. Notably, we also found that after asymptomatic HSV-1 infection, the BBB remains disrupted for up to 30 days when virions are not detectable. We expect that this study will help to better define the possible contribution of HSV-1 infection in multiple sclerosis disease and warrant future studies and trials with antiviral interventions as a potential treatment for this disease to slow its progression.