title: T-Cell tropism of simian varicella virus during primary infection.
abstract: Varicella-zoster virus (VZV) causes varicella, establishes a life-long latent infection of ganglia and reactivates to cause herpes zoster. The cell types that transport VZV from the respiratory tract to skin and ganglia during primary infection are unknown. Clinical, pathological, virological and immunological features of simian varicella virus (SVV) infection of non-human primates parallel those of primary VZV infection in humans. To identify the host cell types involved in virus dissemination and pathology, we infected African green monkeys intratracheally with recombinant SVV expressing enhanced green fluorescent protein (SVV-EGFP) and with wild-type SVV (SVV-wt) as a control. The SVV-infected cell types and virus kinetics were determined by flow cytometry and immunohistochemistry, and virus culture and SVV-specific real-time PCR, respectively. All monkeys developed fever and skin rash. Except for pneumonitis, pathology produced by SVV-EGFP was less compared to SVV-wt. In lungs, SVV infected alveolar myeloid cells and T-cells. During viremia the virus preferentially infected memory T-cells, initially central memory T-cells and subsequently effector memory T-cells. In early non-vesicular stages of varicella, SVV was seen mainly in perivascular skin infiltrates composed of macrophages, dendritic cells, dendrocytes and memory T-cells, implicating hematogenous spread. In ganglia, SVV was found primarily in neurons and occasionally in memory T-cells adjacent to neurons. In conclusion, the data suggest the role of memory T-cells in disseminating SVV to its target organs during primary infection of its natural and immunocompetent host.
authors.affiliation: Department of Viroscience, Erasmus MC, Rotterdam, the Netherlands.
authors.forename: Werner J D
authors.initials: WJ
authors.lastname: Ouwendijk
authors.forename: Ravi
authors.initials: R
authors.lastname: Mahalingam
authors.forename: Rik L
authors.initials: RL
authors.lastname: de Swart
authors.forename: Bart L
authors.initials: BL
authors.lastname: Haagmans
authors.forename: Geert
authors.initials: G
authors.lastname: van Amerongen
authors.forename: Sarah
authors.initials: S
authors.lastname: Getu
authors.forename: Don
authors.initials: D
authors.lastname: Gilden
authors.forename: Albert D M E
authors.initials: AD
authors.lastname: Osterhaus
authors.forename: Georges M G M
authors.initials: GM
authors.lastname: Verjans
mesh_terms: D000818:Animals; D002644:Chickenpox / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D002522:Chlorocebus aethiops; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D014645:Herpesvirus 3, Human; D007150:Immunohistochemistry; D008297:Male; D060888:Real-Time Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000821:virology*