• INCLUSION CRITERIA:

(Participants)

Participants must meet all the following inclusion criteria in order to participate in this study:

1. Children or adults (regardless of age) without known immunocompromise and with a definitively diagnosed severe viral infection, including infection caused by herpesviruses (HSV-1, HSV-2, CMV, EBV, VZV, HHV-6, HHV-7, HHV-8), human papillomavirus (e.g., severe recalcitrant warts), adenovirus, polyomavirus (such as JC virus and BK virus), or influenza virus. Viral infections that would be considered "opportunistic-like", such as herpesvirus esophagitis, herpesvirus encephalitis, CMV colitis, or progressive multifocal leukoencephalopathy (caused by the JC polyoma virus), will be of particular interest in this protocol.

   OR

   Children or adults with a well-documented prior, severe, persistent, or treatment refractory viral infection(s), who have clinically recovered from the viral infection within the past year. If such a patient is not able to visit the NIH for evaluation, his or her personal physician may mail-in blood or other clinical specimens to the NIH for analysis of possible immune defects and for analysis of the virus for mutations, if indicated.

2. Ongoing care by a referring physician.
3. Willingness to allow storage of blood and tissue samples for future analyses.

(Relatives)

Relatives (2 years or above) may be recruited to establish the genetic origin of immune defects that may be identified in the study subjects. We may obtain blood, buccal swabs or a skin biopsy from the relatives.

1. Males and females will be accepted.
2. Adult relatives or the guardians of minor relatives must be willing and capable of providing informed consent after review of protocol procedures that are described in the consent form, with an appropriate study team member.
3. Participating relative agree to have blood stored for future studies of the immune system.

EXCLUSION CRITERIA:

Participants meeting any of the following exclusion criteria at baseline will be excluded from study participation:

1. Patients with previously diagnosed conditions associated with immunodeficiency (e.g., a history of HIV infection or a positive test for HIV) or patients with conditions requiring either daily systemic corticosteroids exceeding a dose equivalent to10 mg/day of prednisone or other significant immunosuppressant therapy (e.g., organ or stem cell transplant recipients).

   Note: Patients will be included if treatment with steroids or other immunosuppressive medication was begun to reduce disease associated with the infection and instituted AFTER the viral disease began.

2. Women who are pregnant.
3. Any condition or major comorbidity that the study investigators believe will compromise the patient's ability to comply with the requirements of the study.