Activation of latent viruses following bone marrow transplantation.
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Biomedical subjects
Publications and source records attributed to C R Rinaldo.
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Mycoplasmal infection leads to a variety of effects on host cells both in vivo and in vitro. Among these is the induction of interferon, which has been demonstrated in mycoplasma-infected human and sheep lymphoreticular cell cultures and in mice. Different species and strains of mycoplasma vary in their ability to induce interferon in these experimental models. Several studies have shown that mycoplasmas do not elicit the production of interferon in murine cells in vitro or in non-lymphoreticular cells of other animal species. This may be related to the ability of host cells to take up mycoplasmas or to mycoplasma-associated products, such as mycoplasmal viruses. Initial studies of mixed infections with mycoplasmas and animal viruses in vivo have demonstrated both an inhibition and an enhancement of viral disease, indicating the complex nature of mycoplasma-animal virus interactions.
Peripheral blood leukocyte and spleen cell cultures derived from adult sheep and from third-trimester (107 to 145 days of gestation) and second-trimester (70 to 98 days of gestation) fetal lambs were examined for their ability to support viral replication and to produce interferon. Bluetongue virus, Herpesvirus hominis type 2, and Chikungunya virus failed to replicate in either leukocyte or spleen cell cultures derived from adult ewes or in cultures from second- or third-trimester fetal lambs. Similarly, peripheral blood leukocytes from adult sheep or third-trimester fetal lambs did not support the replication of Semliki Forest virus, vesicular stomatitis virus, Newcastle disease virus, or vaccinia virus. No major differences were observed in the ability of fetal and adult leukocytes to produce interferon in response to viral infection. In contrast, mean interferon titers induced by bluetongue virus, H. hominis type 2, and Chikungunya virus in spleen cells from second-trimester fetuses were 4- to 10-fold greater than those induced in spleen cells from adult ewes. Variations in interferon levels induced on separate occasions with cells from the same donor age group were observed. The antiviral substance induced in both the fetal and adult cell cultures fulfilled the usual criteria for characterization as interferon.
Interferon was induced in mice after intraperitoneal inoculation with four different mycoplasmas. Peak levels of between 100 and 300 U of interferon per ml were attained by 6 h postinfection with each of the mycoplasmas except Mycoplasma arthritidis, which induced higher titers (400 to 11,800 U/ml) by this time. A fifth mycoplasma, M. pulmonis, induced interferon inconsistently and at a later (72 to 96 h) time. Mycoplasmatales virus MVL51 and sterile mycoplasmal broth did not stimulate interferon production in vivo. All of the mycoplasmas and MVL51 failed to induce interferon in murine spleen cell, peritoneal exudate cell, or peripheral blood leukocyte cultures. Preinfecting the mycoplasmas with MVL51 or treating the organisms with trypsin or dilutions of specific antisera did not enhance their ability to induce interferon in vitro.
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A mycoplasmal species, Acholeplasma laidlawii, isolated as a contaminant from a fetal lamb kidney cell line, was shown to be associated with the induction of interferon in cultures of ovine peripheral blood leukocytes. Broth cultures of the mycoplasma induced between 20 and 230 U of interferon per ml in leukocytes from two adult ewes. The amount of interferon produced correlated with the inoculum size of mycoplasma. Interferon production was associated with replication of the mycoplasma in the leukocyte cultures. Interferon was not induced by sterile mycoplasmal broth, a cell-free filtrate of the mycoplasmal cultures, or heat-inactivated mycoplasmas. The antiviral substance was characterized as interferon by the usual criteria.
OBJECTIVE: To evaluate the role of serum human immunodeficiency virus type 1 immunoglobulin A (HIV-1 IgA) antibodies in the progression of HIV-1 infection in relation to viral load and CD4 cell counts. METHODS: Sequential serum specimens were obtained from 218 homosexual men: 123 HIV-1 seropositives, 24 HIV-1 seroconverters, and 71 HIV-1 seronegatives. HIV-1 IgA antibodies were tested blindly by enzyme-linked immunosorbent assay and Western blot. T-lymphocyte subsets were measured by flow cytometry. Viral plasma load was determined by a sensitive branched DNA assay. RESULTS: HIV-1 IgA antibodies with a titer greater than or equal to 50 were detected among 50% of the seroconverters, 27% of the HIV-1-seropositive asymptomatic subjects, 25% of lymphadenopathy, and 23% of HIV-1-related symptomatic subjects. Among patients with the acquired immune deficiency syndrome, the prevalence of virus-specific IgA antibodies (55%) was significantly higher (p < 0.03) as compared with the HIV-1-seropositive asymptomatic subjects, lymphadenopathy and HIV-1-related symptomatic patients, but not versus the seroconverters (p = 0.8). IgA antibodies to HIV-1 gP160 were the most prevalent among all subjects tested. A significant decrease in CD4 cell counts was observed after HIV-1 seroconversion. Viral load was slightly higher among the seroconverters who demonstrated higher (> or =50) HIV-1 IgA levels. CONCLUSIONS: HIV-1 IgA serum antibodies did not predict the progression of the disease. Correlation between HIV-1 IgA antibodies titer, viral load, and CD4 cell counts was not detected.
Beginning in the latter part of 1985, 2,047 gay and bisexual men who were enrolled in the Pitt Men's Study, the Pittsburgh cohort of the Multicenter AIDS Cohort Study (MACS), were invited by mail to learn the results of their antibody test for HIV infection--human immunodeficiency virus infection. Participants were asked to complete and return a questionnaire designed to assess the factors influencing their (a) decision about learning the results, (b) recent sexual behavior, (c) knowledge about acquired immunodeficiency syndrome (AIDS), and (d) attitudes toward AIDS risk reduction. Of those men, 1,251 (61 percent) accepted the invitation, 188 (9 percent) declined, and 608 (30 percent) failed to respond. Fifty-four percent of the cohort subsequently learned their results. There were no significant differences in demographic, behavioral, and attitudinal characteristics or HIV seroprevalence between the men who accepted and those who declined. However, significant demographic differences were noted between the men who responded to the invitation versus those who did not; the latter group was composed of a greater proportion of men who were younger, nonwhite, and less educated. The most frequently cited reason (90 percent) why men wanted their test results was to determine if they had been infected with HIV. Of those who declined, 30 percent cited concerns about the psychological impact of learning about a positive result as being the most important factor for their decision. The two most frequently selected reasons for declining were the belief that the test is not predictive of the development of AIDS (48 percent) and concern about the worry that a positive result would produce (48 percent). These findings are discussed in the context of a nationwide, voluntary HIV screening program for gay and bisexual men.
To study heterosexual transmission of the human immunodeficiency virus (HIV), 21 HIV antibody-positive hemophiliacs and their 21 spouses-sexual partners were evaluated. None belonged to other AIDS risk groups. HIV antibody was detected in four (19 percent) of the female partners. HIV was isolated from peripheral blood lymphocytes of one hemophiliac (4.8 percent), and one female partner (4.8) was antibody-positive. None of the couples engaged in anal intercourse. Compared with HIV antibody-negative female partners, HIV antibody-positive female partners were younger (P less than .05), had younger hemophiliac partners (P less than .05), and were likely (although not significantly so) to engage in oral sex (P = .08) and to have had more than one sexual partner in the previous 5 years (P = .08). Condoms were used all the time by only eight couples (40 percent), and pregnancy occurred in two other couples (9.5 percent), despite prior counseling. These data confirm the low frequency of heterosexual transmission of HIV from HIV antibody-positive hemophiliacs to their female sexual partners and suggest, moreover, that this may be due to the low rate of HIV infectivity in HIV seropositive hemophiliacs exposed to HIV. Further, these data document the need to design more effective educational programs to prevent heterosexual transmission of HIV.
The significance of chlamydia serum IgG and IgA antibodies was studied, by immunoperoxidase assay, in 210 homosexual men at various stages of HIV infection. Cross sectional analysis of chlamydia IgG antibodies at a titer of > or = 128 indicated a significantly higher prevalence rate among AIDS patients (27.0%) as compared to asymptomatic HIV seronegatives (6.0%) (p = 0.022). The geometric mean titer (GMT) of IgG antibodies to chlamydia was also significantly higher in AIDS patients (106.4) as compared to HIV seronegatives (58.2) (p = 0.022) and persistently asymptomatic HIV seropositives (51.7) (p = 0.05). Chlamydia IgA antibodies did not differ significantly in prevalence and GMT among the various groups.