Systemic and ocular antibody responses to inactivated acute hemorrhagic conjunctivitis (AHC) virus; enterovirus 70 (EV70)

Abstract

Immunization with uv-light inactivated EV70 elicits a classical humoral immune response in rabbits. The protective activity of serum in EV70-infected human conjunctival cells, but not lens cells, was increased by IFN-alpha. Adjuvant MDP-induced conjunctivitis, increased blood-conjunctival barrier (BCB) permeability and anti-EV70 neutralizing activity in tear of seropositive rabbits. The results suggest immunization with inactivated EV70 could provide systemic as well as ocular protection during natural EV70 infection.

Induction of Caspase-dependant Apoptosis by Enterovirus 70 in Human Lens Epithelial SRA01/04 Cells

“…of 1.0 PFU/cell for 18 h or at an m.o.i. of 20 PFU/cell for 7 h, with or without 100 µg/ml guanidine⋅HCl (Gua, a picornavirus RNA synthesis inhibitor [22] which strongly inhibits EV70 RNA synthesis at 100 µg/ml [12] ) ( Fig. 5B and 5D).…”

“…Therefore, the smeared apoptotic DNA ladders in the one-step viral growth experiment may be caused by both apoptosis and necrosis. APOPercentage dye uptake bioassay, according to Biocolor Ltd., is an apoptosis assay that can differentiate apoptosis from necrosis with a sensitivity of one single apoptotic cell [12] . Therefore, to confirm that EV70 induced dose-dependent apoptosis in human lens epithelial cells, confluent SRA01/04 cells in 96-well plates, infected by EV70 at the same concentrations and time as the apoptotic DNA APOPercentage dye uptake bioassay of SRA01/04 cells in 96-well plates, which were treated the same as above, indicated that (a) in the multiple viral growth experiment (1.0 PFU/cell 0 h -18 h), EV70 induced apoptosis level increased with viral infection time prior to 10 h p.i.…”

“…Previously, we have reported that EV70 induced apoptosis at body temperature (37ºC) is an important mechanism for EV70 AHC [12] . At body temperature, whether EV70 infection can cause apoptosis in other permissive human cells and whether EV70 uses the same or different mechanism(s) to induce apoptosis in different human cells, have not yet been determined.…”

“…EV70 can also cause neurological complications (1:10,000) including asymmetrical flaccid motor paralysis (radiculomyelitis) similar to poliomyelitis and cranial nerve palsies as well as a dysautonomic feature [4][5][6][7][8] . Natural and experimental EV70 infection is generally localized to the superficial conjunctival epithelial cell layer (i.e., conjunctivitis) and corneal epithelium (i.e., keratitis) [9,10] and results in AHC. Although it cannot infect and replicate in all kinds of human cells, EV70 has been found to be able to infect and replicate in a broad range of human cells including leukocyte cells (A2.01, Daudi, HL60, Jurkat, Raji, THP-1 and U937) [11] and human eye cells such as HCC cell [12] , SRA01/04 cells [13] , human retina and retina pigment epithelial cells (unpublished).…”

“…Natural and experimental EV70 infection is generally localized to the superficial conjunctival epithelial cell layer (i.e., conjunctivitis) and corneal epithelium (i.e., keratitis) [9,10] and results in AHC. Although it cannot infect and replicate in all kinds of human cells, EV70 has been found to be able to infect and replicate in a broad range of human cells including leukocyte cells (A2.01, Daudi, HL60, Jurkat, Raji, THP-1 and U937) [11] and human eye cells such as HCC cell [12] , SRA01/04 cells [13] , human retina and retina pigment epithelial cells (unpublished). Therefore, EV70 may potentially cause human diseases other than AHC and its neurological complications.…”