Tofacitinib Treatment in Primary Herpes Simplex Encephalitis Interferes With Antiviral Response. 2022

Malgorzata Krzyzowska, and Anders Jarneborn, and Karolina Thorn, and Kristina Eriksson, and Tao Jin
Department of Rheumatology and Inflammation Research, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

Tofacitinib, a Janus kinase inhibitor, is a novel immunosuppressive drug for treatment of rheumatoid arthritis. Herpes simplex virus type 1 (HSV-1) may cause encephalitis during primary infection or following reactivation from a latent state. Long-term tofacitinib treatment may increase the risk of this life-threatening condition. The aim of this study was to investigate the effect of tofacitinib on HSV-1 primary infection using a mouse model. Mice pretreated with tofacitinib were intranasally infected with a clinical strain of HSV-1 and monitored for infection severity and antiviral response. Tofacitinib treatment of HSV-1 primary infection resulted in increased viral loads and worsened clinical outcome. Furthermore, tofacitinib promoted M2 anti-inflammatory phenotype of microglia and infiltrating monocytes, as well as inhibited production of inflammatory and antiviral cytokines by macrophages in vitro. Our findings show that treatment with tofacitinib increases severity of herpes simplex encephalitis in mice, by impairing antiviral response induced by monocytes and microglia.

UI MeSH Term Description Entries
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D010880 Piperidines A family of hexahydropyridines.
D011743 Pyrimidines A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (CYTOSINE; THYMINE; and URACIL) and form the basic structure of the barbiturates.
D006561 Herpes Simplex A group of acute infections caused by herpes simplex virus type 1 or type 2 that is characterized by the development of one or more small fluid-filled vesicles with a raised erythematous base on the skin or mucous membrane. It occurs as a primary infection or recurs due to a reactivation of a latent infection. (Dorland, 27th ed.) Herpes Simplex Virus Infection
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000998 Antiviral Agents Agents used in the prophylaxis or therapy of VIRUS DISEASES. Some of the ways they may act include preventing viral replication by inhibiting viral DNA polymerase; binding to specific cell-surface receptors and inhibiting viral penetration or uncoating; inhibiting viral protein synthesis; or blocking late stages of virus assembly. Antiviral,Antiviral Agent,Antiviral Drug,Antivirals,Antiviral Drugs,Agent, Antiviral,Agents, Antiviral,Drug, Antiviral,Drugs, Antiviral
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D018259 Herpesvirus 1, Human The type species of SIMPLEXVIRUS causing most forms of non-genital herpes simplex in humans. Primary infection occurs mainly in infants and young children and then the virus becomes latent in the dorsal root ganglion. It then is periodically reactivated throughout life causing mostly benign conditions. HSV-1,Herpes Simplex Virus 1,HHV-1,Herpes Simplex Virus Type 1,Herpesvirus 1 (alpha), Human,Human Herpesvirus 1
D020803 Encephalitis, Herpes Simplex An acute (or rarely chronic) inflammatory process of the brain caused by SIMPLEXVIRUS infections which may be fatal. The majority of infections are caused by human herpesvirus 1 (HERPESVIRUS 1, HUMAN) and less often by human herpesvirus 2 (HERPESVIRUS 2, HUMAN). Clinical manifestations include FEVER; HEADACHE; SEIZURES; HALLUCINATIONS; behavioral alterations; APHASIA; hemiparesis; and COMA. Pathologically, the condition is marked by a hemorrhagic necrosis involving the medial and inferior TEMPORAL LOBE and orbital regions of the FRONTAL LOBE. (From Adams et al., Principles of Neurology, 6th ed, pp751-4) Herpes Simplex Encephalitis,Herpetic Acute Necrotizing Encephalitis,Meningoencephalitis, Herpes Simplex Virus,Acute Necrotizing Encephalitis, Herpetic,Herpes Encephalitis,Herpes Simplex Meningoencephalitis,Herpetic Encephalitis,Herpetic Meningoencephalitis,Encephalitides, Herpes Simplex,Encephalitides, Herpetic,Encephalitis, Herpes,Encephalitis, Herpetic,Herpes Simplex Encephalitides,Herpes Simplex Meningoencephalitides,Herpetic Encephalitides,Herpetic Meningoencephalitides,Meningoencephalitides, Herpes Simplex,Meningoencephalitides, Herpetic,Meningoencephalitis, Herpes Simplex,Meningoencephalitis, Herpetic

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