Comparison of Adjuvant Efficacy of Herpes Simplex Virus Type 1 Recombinant Viruses Expressing T_H1 and T_H2 Cytokine Genes

Interactions between Herpesvirus Entry Mediator (TNFRSF14) and Latency-Associated Transcript during Herpes Simplex Virus 1 Latency

“…Plaque-purified HSV-1 strains, the wild-type McKrae expressing LAT [LAT(ϩ)], dLAT2903 [LAT(Ϫ)], and other LAT(Ϫ) viruses, were grown in rabbit skin (RS) cell monolayers in minimal essential medium (MEM) containing 5% fetal calf serum (FCS), as described previously (9,39). Four different LAT(Ϫ) viruses, all derived from HSV-1 McKrae, were used: (i) dLAT2903 has both copies of the LAT promoter (one in each viral long repeat) and the first 1,667 nucleotides (nt) of the LAT transcript deleted (9); (ii) dLAT-gK 3 has LAT nt 76 to 1499 in both copies of LAT replaced by the open reading frame (ORF) encoding HSV-1 glycoprotein K (resulting in the virus containing three copies of gK [gK 3 ]) (40); (iii) dLAT-CD80 contains the complete murine CD80 ORF in place of LAT nt 76 to 1499 in both copies of LAT; and (iv) dLAT-cpIAP contains the complete baculovirus inhibitor of apoptosis protein gene (cpIAP) ORF in place of LAT (15).…”

Recombinant Herpes Simplex Virus Type 1 (HSV-1) Codelivering Interleukin-12p35 as a Molecular Adjuvant Enhances the Protective Immune Response against Ocular HSV-1 Challenge

“…Control vaccines included live viruses that do not result in fatality or produce stromal disease when given peripherally, including HSV-1 strain KOS, a LAT-␥34.5-null mutant of HSV-1 strain McKrae (double mutant parental, dbl-p; Fig. 1B), and a LAT-␥34.5-null mutant expressing IL-4 (vIL-4) (45). Ocular challenge of mice with these recombinant viruses showed that, similar to the parental virus (49) and other recombinant HSV-1 lacking the ␥34.5 gene (8), these recombinant viruses are also attenuated (46).…”

“…In the present study we evaluated the adjuvant effects of each IL-12 subunit separately and together, and we also compared these recombinant viruses with our previously described efficacious recombinant virus that express IL-4 (45). We demonstrate here that these recombinant viruses express IL-12p35 and IL-12p40 in vitro.…”

“…Various cytokines have been used as genetic adjuvants to direct immune responses toward a T H 1 response and away from a T H 2 response (32,40,45,46,52). Recently, we compared adjuvant efficacy of recombinant herpes simplex virus type 1 (HSV-1) expressing T H 1 (i.e., interleukin-2 [IL-2] and gamma interferon [IFN-␥]) and T H 2 (i.e., IL-4) genes in live virus vaccines (45). In that study we showed that IFN-␥-expressing recombinant virus did not exhibit any adjuvant effect.…”

Acute Morphine Administration Reduces Cell-Mediated Immunity and Induces Reactivation of Latent Herpes Simplex Virus Type 1 in BALB/c Mice

“…The WEHI-164 target cells were infected with 5 Multiplicity of Infection (MOI) HSV-1 (KOS) for 4 h and washed three times with the assay medium. CTL activity was measured by the lactate dehydrogenase (LDH) release assay in 96-well round-bottom plates (23). Target cells (2 × 10 4 cells/well) in a 100 l volume were incubated with 100 l of effector cells at various effector/target ratios (10 : 1 or 50 : 1) for 4 h in phenol red-free RPMI 1640 (GIBCO-BRL, UK) medium containing 3% FCS.…”