Immunity to herpes simplex virus type 2: viral antigen-presenting capacity of epidermal cells and its impairment by ultraviolet irradiation

Ia+ epidermal cells (EC) had accessory cell function for herpes simplex virus type 2 (HSV-2)-induced T cell proliferation of immune lymph node cells (LNC). The EC-mediated virus-induced proliferative response of immune LNC was inhibited by ultraviolet B (UVB) irradiation. When EC were pulsed with viral antigen before UVB irradiation, the response was partially restored by addition of epidermal cell-derived thymocyte-activating factor (ETAF). Although normal EC secreted prostaglandin E2, the levels secreted by UVB-irradiated EC were significantly reduced, and the UVB-induced suppression of the proliferative response of immune LNC was not corrected by indomethacin. Soluble factor(s) that suppresses proliferation was generated in supernatants from cultures containing UVB-irradiated but not nonirradiated EC. Sephadex chromatography revealed the presence of factors differentially modulating the proliferative response of HSV-stimulated immune LNC and concanavalin A-stimulated normal lymphoid cells.     

Control of ribonucleic acid function by oligonucleoside methylphosphonates

Oligodeoxyribonucleoside methylphosphonates contain nonionic 3'-5' linked methylphosphonate internucleotide bonds in place of the normal charged phosphodiester linkage of natural nucleic acids. These oligomers are resistant to nuclease hydrolysis, can pass through the membranes of mammalian cells in culture and can form stable hydrogen-bonded complexes with complementary nucleotide sequences of cellular RNAs such as mRNA. The oligomers are readily synthesized on insoluble polymer supports. Their chainlength and nucleotide sequence can be determined by chemical sequencing procedures. Oligonucleoside methylphosphonates which are complementary to the 5'-end, initiation codon region, or coding region of rabbit globin mRNA inhibit translation of the mRNA in rabbit reticulocyte lysates and globin synthesis in rabbit reticulocytes. This inhibition is due to the interaction of the oligomers with mRNA and the extent of inhibition is influenced by the secondary structure of the mRNA and the location of oligomer binding site on the mRNA. Oligomers complementary to the initiation codon regions of N, NS and G protein mRNAs of Vesicular stomatitis virus (VSV) inhibit virus protein synthesis in VSV-infected Mouse L-cells. These oligomers do not affect L-cell protein synthesis or growth. Virus protein synthesis and growth can also be selectively inhibited by oligonucleoside methylphosphonates which are complementary to the donor or acceptor splice junctions of virus pre mRNA. An oligomer complementary to the donor splice junction of SV40 large T antigen mRNA inhibits T-antigen synthesis in SV40-infected African green monkey kidney cells but does not inhibit overall cellular protein synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Immunity to herpes simplex virus type 2 (HSV-2). I. Development of virus-specific lymphoproliferative and leukocyte migration inhibition factor responses in HSV-2-infected guinea pigs

The development of virus-specific cell-mediated immune (CMI) memory and effector response was studied in strain 13/N guinea pigs infected with herpes simplex virus type 2 (HSV-2) (G). The indirect leukocyte migration inhibition factor (LIF) and the lymphocyte transformation (LT) assays, chosen as probable indicators of effector and memory responses, respectively, were performed simultaneously on spleen cells (SC) obtained at varying times after infection and cultured in the presence of uv-inactivated HSV-2 (G) antigen. Kinetic and dose-response analyses revealed: (i) a time-dependent increase in the magnitude and antigen sensitivity of the LT response as well as a time-dependent decrease in the in vitro “doubling time,” both suggestive of immune maturation, and (ii) a biphasic pattern of LIF production in vitro consisting of an “early” component generated within the first 24 hr in culture, and a “late” component detected between 3 and 6 days in culture. “Late” LIF production correlated well with the lymphoproliferative response and appeared to require the presence of glass-adherent cells and active cell division.