title: Ocular infection of mice with an avirulent recombinant HSV-1 expressing IL-4 and an attenuated HSV-1 strain generates virulent recombinants in vivo.
abstract: OBJECTIVE
  To assess the relative impact of overexpression of interleukin 2 (IL-2), interleukin 4 (IL-4), and interferon gamma (IFN-γ) expressing recombinant herpes simplex virus type 1 (HSV-1) on altering immune responses in ocularly infected mice.
  
  
  METHODS
  BALB/c mice were co-infected ocularly with avirulent HSV-1 strain KOS and avirulent recombinant HSV-1 expressing murine IL-4 (HSV-IL-4). Controls mice were co-infected with KOS+HSV-IL-2 or KOS+HSV-IFNγ. Following ocular infection, virus replication in the eye, corneal scarring (CS), and survival were determined. We also isolated recombinant viruses from eye and trigeminal ganglia of KOS+HSV-IL-4 infected mice.
  
  
  RESULTS
  In this study we found that ocular infection of BALB/c mice with a mixture of HSV-IL-4 and KOS resulted in increased death and increased eye disease. In contrast, when mice were infected in one eye with KOS and the other eye with HSV-IL-4 no death or eye disease was seen. Intraperitoneal co-infection of mice with KOS and HSV-IL-4 also did not result in HSV-1 induced death. Interestingly, ocular infection of mice with a mixture of HSV-IL-2 and KOS did not have any effect on severity of the disease in infected mice. We isolated recombinant viruses from KOS+HSV-IL-4 infected mice eye and trigeminal ganglia. Some of the isolated viruses were more neurovirulent then either parental virus. Infection of macrophages with IL-4 expressing virus down-regulated IL-12 production by macrophages.
  
  
  CONCLUSIONS
  These results suggest a role for IL-4 in suppression of immune response and generation of virulent viruses in vivo.
authors.affiliation: Center for Neurobiology and Vaccine Development, Ophthalmology Research Laboratories, CSMC Burns & Allen Research Institute, Los Angeles, CA 90048, USA.
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Mott
authors.forename: Steven L
authors.initials: SL
authors.lastname: Wechsler
authors.forename: Homayon
authors.initials: H
authors.lastname: Ghiasi
mesh_terms: D000818:Animals; D003315:Cornea / Q000473:pathology / Q000821:virology; D015536:Down-Regulation / Q000235:genetics; D005123:Eye / Q000473:pathology / Q000821:virology; D015817:Eye Infections / Q000276:immunology / Q000473:pathology / Q000821:virology*; D005260:Female; D018259:Herpesvirus 1, Human / Q000235:genetics* / Q000302:isolation & purification / Q000472:pathogenicity* / Q000502:physiology; D053765:Interleukin-12 Subunit p35 / Q000235:genetics / Q000378:metabolism; D053762:Interleukin-12 Subunit p40 / Q000235:genetics / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011817:Rabbits; D011995:Recombination, Genetic / Q000235:genetics*; D016019:Survival Analysis; D012668:Trigeminal Ganglion / Q000473:pathology / Q000821:virology; D019562:Viral Load; D014774:Virulence; D014779:Virus Replication
chemical_list: D053765:Interleukin-12 Subunit p35; D053762:Interleukin-12 Subunit p40; D012333:RNA, Messenger; D015847:Interleukin-4