Recombinant herpes simplex virus type 1 expressing murine interleukin-4 is less virulent than wild-type virus in mice.
The effect of interleukin-4 (IL-4) on herpes simplex virus type 1 (HSV-1) infection in mice was evaluated by construction of a recombinant HSV-1 expressing the gene for murine IL-4 in place of the latency-associated transcript (LAT). The mutant virus (HSV-IL-4) expressed high levels of IL-4 in cultured cells. The replication of HSV-IL-4 in tissue culture and in trigeminal ganglia was similar to that of wild-type virus. In contrast, HSV-IL-4 appeared to replicate less well in mouse eyes and brains. Although BALB/c mice are highly susceptible to HSV-1 infection, ocular infection with HSV-IL-4 resulted in 100% survival. Furthermore, 57% of the mice survived coinfection with a mixture of HSV-IL-4 and a lethal dose of wild-type McKrae, compared with only 10% survival following infection with McKrae alone. Similar to wild-type BALB/c mice, 100% of IL-4(-/-) mice also survived HSV-IL-4 infection. T-cell depletion studies suggested that protection against HSV-IL-4 infection was mediated by a CD4(+)-T-cell response.
Ghiasi
H
H
Ophthalmology Research, Cedars-Sinai Burns & Allen Research Institute, Los Angeles, California 90048, USA. ghiasih@CSHS.org
Osorio
Y
Y
Perng
G C
GC
Nesburn
A B
AB
Wechsler
S L
SL
D000818:Animals; D006561:Herpes Simplex / Q000821:virology; D018259:Herpesvirus 1, Human / Q000472:pathogenicity / Q000502:physiology*; D015847:Interleukin-4 / Q000096:biosynthesis / Q000235:genetics*; D051379:Mice; D016865:Reassortant Viruses / Q000472:pathogenicity / Q000502:physiology; D014774:Virulence / Q000235:genetics
D015847:Interleukin-4