Visualizing virus production by resting and activated T cells at transmission and after dissemination to lymphoid tissues.63–65
(A) ISH to detect viral RNA within cells and virions with subsequent TSA reveals virions at the light microscopic level surrounding two kinds of virus-producing cells typed in adjacent tissue sections by combining ISH with staining for cell type and activation state. The long arrow points to a large activated CD4+ T cell (long arrow); the short arrow points to a smaller ostensibly resting T cell lacking markers of activation and proliferation in the cervix of a rhesus macaque following vaginal inoculation of SIV (original magnification 400 × , from reference66). (B). Explosive virus production in a lymph node following dissemination in activated (long arrow) and resting T cells (short arrow). Image suggests clustered virus factories, where virus is efficiently transmitted to susceptible cells in close spatial proximity or through cell-to-cell transmission (long arrow) (original magnification 200 × , image unpublished). Image Credit: Wietgrefe SW and Haase AT. ISH, in situ hybridization; TSA, tyramide signal amplification.