Peripheral blood mononuclear cells harboring viral gene sequences were detected during primary varicellazoster virus (VZV) infection of the human host and the strain 2 guinea pig by in situ hybridization with a 3H-labeled VZV DNA probe. Activated T lymphocytes were permissive for VZV infection at low frequency in vitro.

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SUMMARYStrain 2 guinea-pigs were inoculated with infectious varicella-zoster virus (VZV) or with immunoaflinity-purified proteins of VZV. Monoclonal antibodies to the VZV gpI (90000/58 000 complex) and to a non-glycosylated protein, p170, were used to prepare the polypeptide antigens. Humoral and cell-mediated immune responses to the infectious virus were compared with those elicited by the gpI and p170 proteins. Both VZV IgG antibody production and T lymphocyte proliferation to VZV were detected after immunization with infectious VZV and with VZV proteins. The antibody and T lymphocyte responses waned after protein immunization in comparison with the responses induced by infectious VZV but were detected again immediately after reimmunization with gpI or p170.The study of the pathogenesis of varicella-zoster virus (VZV) infection is hampered by the lack of an appropriate animal model. Simian variceUa virus is antigenically related to human VZV but the disease caused by the former in primates is usually much more severe than VZV infection in the healthy human host (Arvin et al., 1983). Although infection of the guinea-pig with VZV does not produce disease, Myers et al. (1985) observed that human VZV passaged in foetal guinea-pig tissue culture caused viraemia and nasopharyngeal infection in weanling guinea-pigs. Antibodies to viral proteins of 62000, 98000 and 118000 Mr detected by immunoprecipitation with sera from VZV-immune human subjects were also observed by immunoprecipitation with guinea-pig sera (Grose & Friedrichs, 1982). Matsunaga et al. (1982) showed that guinea-pigs inoculated with VZV adapted to guinea-pig cells developed delayed hypersensitivity to VZV antigen as well as VZV-specific antibodies.In the present study, the immunogenic potentials of a major VZV glycoprotein, gpI (Davison et al., 1986), and of a non-glycosylated protein, p170, were evaluated in the strain 2 guinea-pig and compared with the immune response after inoculation with infectious VZV. The strain 2 guinea-pig was used for these immunological studies because of its potential value for the study of VZV pathogenesis in relation to the immune response.The animals were weanling strain 2 guinea-pigs obtained from the Charles River Caviary, Charles River Breeding Laboratories, Wilmington, Mass. and the National Cancer Institute, Bethesda, Md., U.S.A. and weighed approximately 250 g at the time of the initial inoculation. The animals that received infectious VZV were inoculated with guinea-pig-adapted VZV. Foetal guinea-pig cell lines were established from guinea-pig embryos of 1.0 to 1-5 cm (Edmond et al., 1981). The cells were grown in ME M with 10 ~ foetal calf serum and were used to prepare VZV-infected cells for up to six passages. A VZV isolate from a cutaneous varicella vesicle was passed ten times in guinea-pig embryo cells. Guinea-pig cell-adapted VZV was stored at -70 °C and passed once more in guinea-pig embryo cells immediately before use. Animals given 0000-7694 © 1987 SGM

The rate of collagen synthesis was measured in vivo and in vitro in both normal and damaged mouse lung tissue. Acute lung damage was induced by the administration of butylated hydroxytoluene (BHT). The production of labeled hydroxyproline, following the administration of labeled proline, was used as an index of collagen production. Total and labeled hydroxyproline in normal and damaged lung tissue were solubilized equally following digestion with purified collagenase. Assuming that the extent of hydroxylation was not altered, this indicated that hydroxyproline was an accurate index of collagen content and production in damaged as well as normal lung tissue. The quantities of hydroxyproline formed at various times both in vivo and in vitro were calculated from the specific activity of free proline in lung tissue. The specific activity of free proline in normal and damaged lung tissue remained constant in vivo for at least 90 minutes after the intravenous injection of labeled proline. Hydroxyproline production was a linear function of time for up to 90 minutes in vivo and three hours in vitro. The in vivo rate of hydroxyproline production was significantly greater than the in vitro rate in lung tissue from similarly treated mice. The difference ranged from five-fold in normal lung tissue to eight-fold in lung tissue damaged by the administration of BHT. Comparable differences were seen between the in vivo and in vitro rates of non-collagen protein synthesis. Despite these differences in rates, the percentage of total protein synthesis committed to collagen in vivo was the same as in vitro in normal lung, and identical increases were seen in damaged lung. These data show that in vivo rates of both collagen and non-collagen protein synthesis are significantly higher than those measured in mouse lung tissue in vitro. Although the relative increases in collagen synthesis that occur in response to lung damage are larger in vivo, measurements of collagen synthesis in vitro do accurately reflect the general changes that accompany acute lung damage.