Specific and nonspecific immune stimulation of MHC-II-deficient mice results in chronic HSV-1 infection of the trigeminal ganglia following ocular challenge

Ocular herpes simplex virus type 1 (HSV-1) infection of MHC-II-deficient mi ce (A(beta)(O/O) mice) or their parental C57BL/6J wild-type mice resulted i n the establishment of typical HSV-I latent infections in the trigeminal ga nglia (TG) of the surviving mice by day 28 postinfection. Latency was chara cterized by the complete absence of infectious virus in TG extracts, the ab ility to recover latent virus only following prolonged tissue culture culti vation of explanted TG, and the presence of HSV-1 DNA in TG extracts. When mice were vaccinated prior to ocular HSV-1 challenge, latency appeared unal tered in the C57BL/6J wild-type mice. However, in A(beta)(O/O) mice, cleara nce of virus from the TG appeared to be seriously impaired, resulting in a chronic productive infection, rather than a latent infection. infectious vi rus was readily detected in TG extracts of vaccinated A(beta)(O/O) mice unt il at least 63 days postinfection. Glycoprotein B mRNA was also readily det ected, confirming continued viral transcription. These chronic infections o ccurred regardless of whether the A(beta)(O/O) mice were vaccinated with HS V-1-specific antigens (i.e., live HSV-1 strain KOS, recombinantly expressed HSV-1 glycoprotein D plus Freund's adjuvant, or a mixture of seven recombi nantly expressed HSV-1 glycoproteins plus adjuvant) or non-HSV-1-specific a ntigens (i.e., tissue culture medium plus 5% fetal bovine serum, the expres sion vector plus adjuvant, or adjuvant alone). Passive transfer of HSV-1 ne utralizing antibody to vaccinated A(beta)(O/O) mice between days 0 and 28 p ost-ocular challenge did not clear infectious virus from the TG. Passive tr ansfer of anti-HSV-1 antibody or purified naive mouse serum to unvaccinated A(beta)(O/O) mice on days 3 or 6 post-HSV-1 ocular challenge also resulted in chronic, rather than latent, infection of the TG, Passive transfer of n aive sera from B-cell-deficient mice or injection of keyhole limpet hemocya nin or purified IgG, but not PBS or dextran, 3 days after HSV-1 challenge a lso resulted in chronic infection of the TG. (C) 1999 Academic Press.