The viral persistence infection becomes a major problem of public health in terms of the viral epidemic because many of the persistently infected individuals might not show any clinical symptom. The incidences of persistency in different viruses are varied. The highest rate of persistent viral infection is Hepatitis C virus ( HCV) which has been reported for 60-80% of the acutely infected patients. This causes the difficulty to the global public health to prevent viral transmission and epidemic. This article proposes a perspective to explain that viral persistence is associated with the appearance of the MHC allele molecules in each person. This relates to the process to induce the appropriate adaptive immunity, especially the effective cytotoxic T cell clone(s), to clear the entire infected virus from the infected host. The comprehension of the viral pathogenesis concerning viral persistence is the fundamental issue to prevent the viral epidemic and further search for an effective strategy to treat the viral persistence infection in the future.