![]() ![]() In this review, we discuss primary immunodeficiencies that predispose individuals to severe viral infections in the presence or absence of an increased susceptibility to severe disease with other pathogens. Such patients present with infections that are severe, persistent, recurrent, or refractory to therapy and are usually caused by viruses of low virulence prevalent in the community. ![]() For individuals who are immunocompromised, because of a genetic immunodeficiency or immunosuppressive drug therapy, viral infections may result in life-threatening disease. These individuals are able to mount effective immune responses that either clear the virus from the body or, for viruses that establish latency, maintain the virus in a dormant state. The majority of viral infections acquired by nonimmunosuppressed individuals are asymptomatic or result in mild clinical manifestations. Undoubtedly, additional mutations in proteins in the innate and adaptive arms of the immune system will be identified in the future, which will reveal the importance of these proteins in controlling infections caused by viruses and other pathogens. These immunodeficiencies are rare, but it is important to identify them both for prognostic information and for genetic counseling. Although the role of cytotoxic T cells in controlling viral infections is well known, a number of immunodeficiencies that predispose to severe viral diseases have recently been ascribed to defects in the Toll-like receptor–interferon signaling pathway. Some immunodeficiencies enhance susceptibility to disease with a specific virus or family of viruses, whereas others predispose to diseases with multiple viruses in addition to disease with other microbes. In this review, we summarize primary immunodeficiencies that predispose individuals to severe viral infections. ![]() Patients with severe viral infections are often not thoroughly evaluated for immunodeficiencies. ![]()
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