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They may prime the reactivity to drugs in <jats:italic>two<\/jats:italic> ways: <jats:italic>First, by virus\u2010induced second signals:<\/jats:italic> certain drugs like \u03b2\u2010lactam antibiotics are haptens and covalently bind to various soluble and tissue proteins, thereby forming novel antigens. Under homeostatic conditions, these neo\u2010antigens do not induce an immune reaction, probably because co\u2010stimulation is missing. During a virus infection, the hapten\u2010modified peptides are presented in an immune\u2010stimulatory environment with co\u2010stimulation. A drug\u2010specific immune reaction may develop and manifest as exanthema. <jats:italic>Second, by increased pharmacological interactions with immune receptors (p\u2010i)<\/jats:italic>: drugs tend to bind to proteins and may even bind to immune receptors. Without viral infections, this low affine binding may be insufficient to elicit T\u2010cell activation. During a viral infection, immune receptors are more abundantly expressed and allow more interactions to occur. This increases the overall avidity of p\u2010i reactions and may even be sufficient for T\u2010cell activation and symptoms. There is a situation where the virus\u2010DHR sequence of events is inversed: in drug reaction with eosinophilia and systemic symptoms (DRESS), a severe DHR can precede reactivation and viremia of various herpes viruses. One could explain this phenomenon by the massive p\u2010i mediated immune stimulation during acute DRESS, which coincidentally activates many herpes virus\u2010specific T cells. Through p\u2010i stimulation, they develop a cytotoxic activity by killing herpes peptide\u2010expressing cells and releasing herpes viruses. These concepts could explain the often transient nature of DHR occurring during viral infections and the often asymptomatic herpes\u2010virus viraemia after DRESS.<\/jats:p>","DOI":"10.1111\/all.15558","type":"journal-article","created":{"date-parts":[[2022,10,20]],"date-time":"2022-10-20T14:38:36Z","timestamp":1666276716000},"page":"60-70","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["Viral infections and drug hypersensitivity"],"prefix":"10.1111","volume":"78","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8117-359X","authenticated-orcid":false,"given":"Werner J.","family":"Pichler","sequence":"first","affiliation":[{"name":"ADR\u2010AC GmbH  Bern Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8607-6254","authenticated-orcid":false,"given":"Marie\u2010Charlotte","family":"Br\u00fcggen","sequence":"additional","affiliation":[{"name":"Allergy Unit, 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