title: Delayed control of herpes simplex virus infection and impaired CD4(+) T-cell migration to the skin in mouse models of DOCK8 deficiency.
abstract: DOCK8 deficiency in humans and mice leads to multiple defects in immune cell numbers and function. Patients with this immunodeficiency have a high morbidity and mortality, and are distinguished by chronic cutaneous viral infections, including those caused by herpes simplex virus (HSV). The underlying mechanism of the specific susceptibility to these chronic cutaneous viral infections is currently unknown, largely because the effect of DOCK8 deficiency has not been studied in suitable models. A better understanding of these mechanisms is required to underpin the development of more specific therapies. Here we show that DOCK8-deficient mice have poor control of primary cutaneous herpes simplex lesions and this is associated with increased virus loads. Furthermore, DOCK8-deficient mice showed a lack of CD4(+) T-cell infiltration into HSV-infected skin.
authors.affiliation: Research School of Biology, Australian National University, Canberra, Australian Capital Territory, Australia.
authors.forename: Inge E A
authors.initials: IE
authors.lastname: Flesch
authors.affiliation: 1] John Curtin School of Medical Research, Australian National University, Canberra, Australian Capital Territory, Australia [2] ANU Medical School, Australian National University, Canberra, Australian Capital Territory, Australia.
authors.forename: Katrina L
authors.initials: KL
authors.lastname: Randall
authors.affiliation: Research School of Biology, Australian National University, Canberra, Australian Capital Territory, Australia.
authors.forename: Natasha A
authors.initials: NA
authors.lastname: Hollett
authors.affiliation: 1] John Curtin School of Medical Research, Australian National University, Canberra, Australian Capital Territory, Australia [2] ANU Medical School, Australian National University, Canberra, Australian Capital Territory, Australia.
authors.forename: Hsei
authors.initials: H
authors.lastname: Di Law
authors.affiliation: John Curtin School of Medical Research, Australian National University, Canberra, Australian Capital Territory, Australia.
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Miosge
authors.affiliation: John Curtin School of Medical Research, Australian National University, Canberra, Australian Capital Territory, Australia.
authors.forename: Yovina
authors.initials: Y
authors.lastname: Sontani
authors.affiliation: John Curtin School of Medical Research, Australian National University, Canberra, Australian Capital Territory, Australia.
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Goodnow
authors.affiliation: Research School of Biology, Australian National University, Canberra, Australian Capital Territory, Australia.
authors.forename: David C
authors.initials: DC
authors.lastname: Tscharke
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D002634:Chemotaxis, Leukocyte / Q000235:genetics / Q000276:immunology; D004195:Disease Models, Animal; D020662:Guanine Nucleotide Exchange Factors / Q000172:deficiency*; D006561:Herpes Simplex / Q000235:genetics* / Q000276:immunology* / Q000473:pathology / Q000821:virology; D007109:Immunity; D051379:Mice; D018345:Mice, Knockout; D018139:Simplexvirus / Q000276:immunology*; D012867:Skin / Q000276:immunology* / Q000473:pathology* / Q000821:virology; D019562:Viral Load
chemical_list: C545324:Dock8 protein, mouse; D020662:Guanine Nucleotide Exchange Factors