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The effects of human leukocyte interferon on BK papovavirus (BKV) infection in 41 recipients of renal transplants were studied as part of a randomized, double-blind, placebo-controlled trial. Eight transplant recipients demonstrated fourfold or greater rises in antibody to BKV, and three excreted BKV in urine. Neither seroconversion nor excretion was reduced by interferon administration. No clinical syndromes could be clearly linked to BKV infection. BKV was also relatively resistant to the in vitro effects of interferon. Pretreatment of interferon-sensitive human fibroblasts with up to 620 units of interferon/ml resulted in a loss of viral infectivity of one log or less. Continuous exposure of infected cultures to these interferon levels reduced BKV titers by 1.5-2.9 logs, whereas continuous exposure to lower concentrations of interferon had less effects. The levels shown to be marginally effective in vitro were considerably higher than those achieved in these patients' sera.

Over the past decade a growing number of reports have appeared in the literature attesting to the frequent occurrence and clinical significance of cytomegalovirus (CMV) infection in recipients of tissue transplants. Although such infections have been most extensively studied among recipients of kidney and bone marrow transplants, recent studies have confirmed the ubiquity and potential seriousness of this infection among cardiac transplant patients as well. Two patterns of CMV disease have been noted: (1) primary CMV disease, in which the transplant recipient has had no previous experience with the virus (and is seronegative for CMV before the transplant) and develops infection with virus that appears to be transmitted in latent fashion with an allograft from a seropositive donor; and (2) reactivation disease, in which the transplant recipient, who has been infected with CMV previously (and is seropositive for CMV before the transplant), reactivates endogenous latent virus. In both instances, the immunosuppressive therapy required for transplantation and the rejection processes that follow placement of an allograft appear to activate latent virus and make it clinically manifest. Currently available data would

Cytomegalovirus (CMV) produces a latent infection in its host. The actively or latently infected transplanted kidney and heart are sources of debilitating CMV infection in transplant recipients [1], but the organs and cellular sites of viral latency and the mechanisms of CMV activation have not been fully defined. Latent murine cytomegalovirus (MCMV) has been activated in vitro by cocultivating spleen cells or peritoneal macrophages with allogeneic, syngeneic, or both mouse embryo cultures (MECs) [2-5]. MCMV has also been activated from explant cultures of spleens and prostate glands, cultured with or without MECs [6, 7]. Cultures of salivary glands, liver, kidney, and brain from latently infected mice, however, have failed to yield MCMV in vitro [8]. Latently infected, heterotopic cardiac isografts are the source of lethal MCMV infection in the immunosuppressed recipient [9]. Results presented below demonstrate the activation of latent MCMV from cardiac explants and dissociated cardiac cell cultures when cultured alone or with allogeneic MECs. The Smith strain of MCMV was maintained in this laboratory by serial passage of CD-1 Swiss mice (Charles River Breeding Laboratory, Wilmington, Mass) followed by salivary gland harvest as described elsewhere [9]. The stock virus had a titer of 2 x 10' pfu/ml. Noninfected salivary gland homogenates (NSG) were prepared in a similar manner after inoculation of weanling mice with saline. Virus stocks and NSG were stored at 70 C until use. Latent infection was established by ip inoculation of five-weekold female BALB/c mice (Cumberland View Farms, Clinton, Tenn) with 104 pfu of MCMV (0.1 ml of infected salivary gland homogenate). These mice were then maintained in our animal facility for four to six months, at which time their hearts were used for tissue culture. Control animals had been injected with an equal volume of NSG and maintained for four to six months in the same way. These animals showed no evidence of virus by salivary gland culture or by antibody testing at the time of death. Explants of cardiac tissue were prepared by aseptically removing hearts from latently infected or NSG-inoculated mice and placing them in cold, lactated Ringers solution with 507o dextrose. Hearts were transferred into petri dishes containing fresh Ringers solution and cut into 1x 2-mm pieces that were kept on ice. Secondary MECs (prepared as previously described [9] from pathogen-free CD-1 Swiss mice) seeded the previous day in six-well plates (Falcon Plastics, Oxnard, Calif) containing RPMI medium with

Infections due to BK papovavirus frequently occur in renal transplant recipients [2] and may be involved in a variety of syndromes, including ureteral obstruction, deterioration of graft function, and pancreatic disease. The source of the BK papovavirus in these cases is not clear. Because the renal allograft has been implicated as a source of primary cytomegalovirus infections in renal transplant recipients [3], we investigated the possibility that donor kidneys may also contribute to the transmission of BK papovavirus. A fourfold or greater increase in titers of HAI antibodies to BK papovavirus was observed in 55 (24%) of 230 renal transplant recipients. Seronegative recipients who received kidneys from seropositive donors were 3.5 times more likely to develop an infection due to BK papovavirus than were seronegative recipients of kidneys from seronegative donors. The antibody status of the donor did not affect the likelihood of an increase in titers of antibody to BK papovavirus in seropositive recipients. These results suggest that BK papovavirus may be transmitted with transplanted kidneys and that transplant recipients who are at risk for primary infection by this route are more than twice as likely to have increased titers of antibody to BK papovavirus as those who are at risk for the reactivation of an infection. Further studies should be performed to define the relative role of cadaver vs. living, related kidney donors in the transmission of BK papovavirus and the clinical syndromes that are related to primary and reactivated infections.

L'insuffisance renale chronique et l'hemodialyse ne modifient pas significativement la pharmacocinetique de l'interferon leucocytaire exogene a faible dose. Des modifications de la posologie sembleraient inutiles pour les malades avec une insuffisance renale chronique, qu'ils soient ou non soumis a l'hemodialyse