Establishment of latent herpes simplex virus type 1 infection in resistant, sensitive, and immunodeficient mouse strains

Productive infection with herpes simplex virus (HSV) type 1 is limited by b oth innate and adaptive immune mechanisms. The purpose of the current study was to determine whether these mechanisms also play a role in the establis hment of latent HSV infection. First we examined the trigeminal ganglia (TG ) of severe combined immunodeficiency (SCID), interferon-gamma knockout (GK O), and beige (a strain deficient in natural killer cell activity) mice fol lowing ocular inoculation with HSV. Although infection of SCID mice was inv ariably lethal, we consistently found latently infected neurons in the TG o f these animals at 2-4 days postinoculation. HSV infection of GKO and beige mice, while not lethal, was characterized by a greater number of productiv ely infected TG neurons and/or a delay in the time to peak productive infec tion compared to C57BL/6 controls. However, as assayed by both in situ hybr idization for LAT expression and quantitative PCR (Q-PCR) for viral DNA, we found that HSV established a latent infection in GKO and beige mice as eff iciently as in C57BL/6 controls. We subsequently examined the TG of "HSV-se nsitive" strains of mice (Swiss-Webster, CBA, and BALB/c) following ocular infection with HSV. At the peak of acute ganglionic infection the number of productively infected TG neurons in each of these mouse strains was about sevenfold greater than in the "HSV-resistant" strain C57BL/6, consistent wi th previously reported differences in susceptibility to lethal challenge wi th HSV. However, as assayed by both in situ hybridization for LAT and Q-PCR for viral DNA, we found that HSV established a latent infection in Swiss-W ebster, CBA, and BALB/c mice as efficiently as in C57BL/6 controls. We conc lude that HSV efficiently establishes latent infection in the TG of mice in the absence of innate and adaptive immune mechanisms that are essential fo r limiting productive viral infection. (C) 2000 Academic Press.