Showing papers on "Viremia published in 1988"

Molecular Analysis of Virus and Leukocyte Interactions in Viremia

Abstract: Viremia is a hallmark ofdisseminated cytomegalovirus (CMV) infection and disease. Using conventional virus culture and a subgenomic cloned CMV DNA probe to detect viral DNA within leukocytes, we studied the virus-cell interactions involved in immunocompromised patients with viremicCMV infection. CMV was recovered by culture in 17/17 samples enriched for polymorphonuclear leukocytes. Viral DNA was detected by dot-blot hybridization in 16/17 (94%). In contrast, samples enriched for mononuclear cells yielded infectious CMV in culture in only 7/15 (47%) instances; nonetheless, viralDNA was present in 16/17 samples probed. The quantity of CMV DNA in polymorphonuclear cells was significantly greater than in mononuclear leukocytes (mean 13.1 vs. 9.1 estimated viral genome equivalents per 100 cells, respectively), andCMV was always recovered from these cells regardless of the amount of viral DNA present. Yet, when the amounts of CMVDNA were virtually identical in granulocytes and mononuclear cells (6.3 and 7.1 genomic equivalents, respectively) collected simultaneously, infectious CMV could not be recovered from mononuclear cells. Although several interpretations are possible, these data are consistent with the view thatCMV exists within granulocytes in a mature infectious form during viremia. The virus interactions with mononuclear cells appear to be more complex, particularly in those cells that contain CMVDNA but do not yield infectious virus.

Disseminated cytomegalovirus infection. Molecular analysis of virus and leukocyte interactions in viremia.

Abstract: Viremia is a hallmark of disseminated cytomegalovirus (CMV) infection and disease. Using conventional virus culture and a subgenomic cloned CMV DNA probe to detect viral DNA within leukocytes, we studied the virus-cell interactions involved in immunocompromised patients with viremic CMV infection. CMV was recovered by culture in 17/17 samples enriched for polymorphonuclear leukocytes. Viral DNA was detected by dot-blot hybridization in 16/17 (94%). In contrast, samples enriched for mononuclear cells yielded infectious CMV in culture in only 7/15 (47%) instances; nonetheless, viral DNA was present in 16/17 samples probed. The quantity of CMV DNA in polymorphonuclear cells was significantly greater than in mononuclear leukocytes (mean 13.1 vs. 9.1 estimated viral genome equivalents per 100 cells, respectively), and CMV was always recovered from these cells regardless of the amount of viral DNA present. Yet, when the amounts of CMV DNA were virtually identical in granulocytes and mononuclear cells (6.3 and 7.1 genomic equivalents, respectively) collected simultaneously, infectious CMV could not be recovered from mononuclear cells. Although several interpretations are possible, these data are consistent with the view that CMV exists within granulocytes in a mature infectious form during viremia. The virus interactions with mononuclear cells appear to be more complex, particularly in those cells that contain CMV DNA but do not yield infectious virus.

Efficacy of S26308 against guinea pig cytomegalovirus infection.

Abstract: Prophylactic use of antiviral agents against cytomegalovirus (CMV) is particularly indicated for the immunocompromised host because morbidity and mortality due to CMV occur most frequently following immunosuppression. We have evaluated the new Riker compound S26308 for its therapeutic and prophylactic antiviral activity against CMV in guinea pigs. The efficacy of the compound was assessed in vitro in guinea pig embryo cells and in vivo in both immunocompetent and immunocompromised guinea pigs. Guinea pig CMV plaque formation was reduced only in cells treated with S26308 prior to virus infection. The antiviral activity remained even when the compound was removed after virus absorption and was due to neither virus destruction nor inhibition of cell growth. The frequency of viremia was reduced in guinea pigs for which S26308 therapy was initiated 24 h prior to virus inoculation compared with sham-treated animals. This reduction in the frequency of viremia did not prevent virus spread to target tissues but did result in a reduction of the severity of CMV-induced disease in immunocompromised guinea pigs. Low levels of interferon were detected in supernatants of S26308-treated cells, and interferon was detected in the serum of guinea pigs given S26308. These results indicate that S26308 can induce interferon and reduce CMV infectivity in vivo and in vitro when used prophylactically. This antiviral activity, although modest, was accompanied by beneficial effects on CMV-induced morbidity and mortality. Prophylactic use of S26308 in combination with other therapeutic agents may be a useful strategy against CMV infections.

Olfactory neural pathway in mouse hepatitis virus nasoencephalitis.

Abstract: The mechanism of brain infection with mouse hepatitis virus-JHM was studied in BALB/cByJ mice following intranasal inoculation, and found to be a consequence of direct viral spread along olfactory nerves into olfactory bulbs of the brain. Infection was followed sequentially from nose to brain, using microscopy, immunohistochemistry and virus quantification. Lesions, antigen and virus were observed in the olfactory bulb and anterior brain as early as 2 days and posterior brain by 4 days after inoculation. Viral antigen extended through nasal mucosa into submucosa, then coursed along the olfactory nerve perineurium and fibers, through the cribriform plate into the olfactory bulbs. On days 4 and 7, viral antigen was found in the antero-ventral brain, along ventral meninges, olfactory tracts and anterior ramifications of the lateral ventricles. Virus was cleared from nose by 10 days and anterior brain by 20 days, but persisted in posterior brain for 20 days after inoculation. Mice also developed disseminated infection, with viremia and hepatitis. Infection of brain did not correlate with presence of viremia. In contrast to intranasally inoculated mice, orally-inoculated mice did not develop encephalitis, despite evidence of disseminated infection.

Effect of human gamma interferon on yellow fever virus infection.

Abstract: We studied yellow fever virus infection in two species of monkey: Saimiri sciureus (squirrel monkeys) and Macaca mulatta (rhesus monkeys) Human gamma interferon was administered intravenously in five equal doses, one was given 24 hr before infection followed by four doses 24 hr apart Interferon reduced the levels and duration of viremia and the severity of hepatitis in squirrel monkeys Interferon prolonged survival time and delayed the appearance of viremia and hepatitis in infected rhesus monkeys, but it did not change overall mortality

Maternal transmission of retroviral disease: transgenic mice as a rapid test system for evaluating perinatal and transplacental antiretroviral therapy

Abstract: Transgenic mouse strains carrying Moloney murine leukemia virus (Mo-MuLV) in the germ line were found to serve as rapid and quantitative models of in utero and perinatal retroviral infection for evaluating strategies of antiretroviral therapy In these strains virus activation leads to virus expression, viral spread associated with the development of viremia, and subsequent T-cell leukemia/lymphoma To test these transgenic strains for their usefulness in evaluating antiretroviral agents, the effect of the drug 3'-azido-3'-deoxythymidine (AZT) on the development of viremia and subsequent disease was examined The assessment of mice for viremia at 1 month of age appeared to be the most useful assay because it was rapid and quantitative AZT was most effective in preventing viremia in transgenic strains that activate Mo-MuLV after birth and had more variable effects in strains that activate prior to birth However, in six of seven of the strains examined, AZT led to a marked improvement in survival and reduced the onset of T-cell leukemia/lymphoma These results provide evidence for effective antiretroviral therapy during gestation and in the perinatal period and are of potential significance for the management of the maternal transmission of human retroviruses

Moderately virulent African swine fever virus infection: blood cell changes and infective virus distribution among blood components.

Abstract: Blood samples of pigs infected with a moderately virulent African swine fever virus (ASFV) isolate, obtained from the Dominican Republic (DR-II), were monitored temporally for viremia, infective ASFV association with major blood components, differential changes in blood cell composition, and plasma antibodies to ASFV. After intranasal/oral virus inoculation, pigs underwent acute infection and illness that resolved. Acute illness began on postinoculation day (PID) 4 and continued to PID 11, and pigs were febrile, with maximal infective ASFV titers detected in blood. By PID 11, initial antibody titers to ASFV antigens were detected in plasma. The WBC numbers were maintained near preinoculation counts; however, lymphocyte counts decreased slightly with a compensatory increment in neutrophil and monocyte numbers. From PID 11 to PID 25, rectal temperatures gradually returned to preinoculation values, titers of viremia began to decrease, plasma antibody to ASFV antigens increased to peak titers, and WBC numbers increased slightly. Percentages of lymphocytes returned to preinoculation values, neutrophil percentages decreased to slightly below preinoculation values, monocyte percentages were mildly increased, and eosinophil percentages were unaffected. From PID 25 to PID 46, titers of viremia further decreased, and plasma titers of antibodies to ASFV antigens remained high. In pigs with DR-II viremia (PID 4 to PID 46), most viral infectivity (greater than 95%) was RBC associated. Plasma contained less than 1% infectivity, and less than 0.1% of virus was in the WBC fraction (monocytes, lymphocytes, and granulocytes). After PID 46, viremia was no longer detectable.

Uptake of reovirus serotype 1 by the lungs from the bloodstream is mediated by the viral hemagglutinin.

Abstract: We used the mammalian reoviruses to determine the molecular basis of the clearance of a virus from the bloodstream by specific organs. Reovirus serotypes 1 (T1) and 3 (T3) were radiolabeled with [35S]methionine or 125I, and the viruses were injected intravenously into weanling rats. The distribution of radioactivity within the animals was determined at various times after the injection. Both viruses were cleared rapidly from the bloodstream and concentrated in different organs. Reovirus T1 was found predominantly in the lungs and liver, whereas T3 was found predominantly in the liver, with very little virus in the lungs. Using intertypic reassortants, we determined that the T1 S1 gene, which encodes the viral hemagglutinin (sigma 1 protein), is responsible for the difference in uptake of T1 and T3 by the lungs. The genetic mapping was extended by using several approaches. (i) T1 subjected to limited proteolytic digestion with chymotrypsin was cleared efficiently by the lungs despite the removal of sigma 3 and digestion of mu 1C to delta. (ii) Uptake of T1 by the lungs was totally inhibited by incubation of T1 with an anti-sigma 1 monoclonal antibody or its Fab fragment before injection. (iii) A reovirus T1 variant in the sigma 1 protein was poorly taken up by the lungs. These data indicate that clearance of reovirus from the bloodstream by the lungs is dependent on the presence of the T1 sigma 1 protein.

Feline leukemia/sarcoma viruses and immunodeficiency.

Abstract: Publisher Summary This chapter discusses the structure feline leukemia virus (FeLV) and pathogenesis of lymphomas and leukemias BY FeLV. FeLV is quite similar to the better-studied murine leukemia viruses in structure and genetic map. The virus particles bud from cytoplasmic membranes into either extracellular spaces or into vacuoles. FeLV has long been considered a typical noncytopathogenic, longlatency leukemia virus based on its behavior in fibroblasts in vitro . Recent evidence suggests that its in vivo behavior in critical target hemolymphatic tissues is as likely to be cytopathic as transforming. The type of FeLV-related disease that occurs and the disease-free interval probably are influenced by viral envelope proteins and glycoproteins and the consequences of proviral integration. FeLV subgroup specificity apparently determines when and what type of disease will occur. The ecotropic FeLV-A is the most frequent subgroup found in pet cats and is transmitted contagiously. Immunosuppression is the most frequent and the most devastating manifestation of FeLV viremia in clinical and experimental studies. It seems that multiple cell types and multiple processes are involved in the development of feline retrovirus-induced immunosuppression. Although no solid evidence is available for the malfunctioning of cat T helper cells because of the paucity of T-cell specific markers, the circumstantial evidence provided thus far indicates an impaired T helper function in FeLV-infected cats similar to that observed in humans infected with HIV. Studies on the pathogenesis of FeLV-induced immunosuppression might provide a valuable mode for a better understanding and means of control of human AIDS.