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T W Baba

Publications and source records attributed to T W Baba.

29 records · Page 2Linked to original sources
PubMed1995

Pathogenicity of live, attenuated SIV after mucosal infection of neonatal macaques.

Adult macaques do not develop disease after infection with a nef deletion mutant of the simian immunodeficiency virus (SIV) and are protected against challenge with pathogenic virus. This finding led to the proposal to use nef-deleted viruses as live, attenuated vaccines to prevent human acquired immunodeficiency syndrome (AIDS). In contrast, neonatal macaques developed persistently high levels of viremia after oral exposure to and SIV nef, vpr, and negative regulatory element (NRE) deletion mutant. Severe hemolytic anemia, thrombocytopenia, and CD4+ T cell depletion were observed, indicating that neither nef nor vpr determine pathogenicity in neonates. Because such constructs have retained their pathogenic potential, they should not be used as candidate live, attenuated virus vaccines against human AIDS.

AIDS Vaccines↗
PubMed1995

Apoptosis occurs predominantly in bystander cells and not in productively infected cells of HIV- and SIV-infected lymph nodes.

Although 13 years have passed since identification of human immunodeficiency virus-1 (HIV-1) as the cause of AIDS, we do not yet know how HIV kills its primary target, the T cell that carries the CD4 antigen. We and others have shown an increase in the percentage of apoptotic cells among circulating CD4+ (and CD8+) T cells of HIV-seropositive individuals and an increase in frequency of apoptosis with disease progression. However, it is not known if this apoptosis occurs in infected or uninfected T cells. We show here, using in situ labelling of lymph nodes from HIV-infected children and SIV-infected macaques, that apoptosis occurs predominantly in bystander cells and not in the productively infected cells themselves. These data have implications for pathogenesis and therapy, namely, arguing that rational drug therapy may involve combination agents targeting viral replication in infected cells and apoptosis of uninfected cells.

Animals↗
PubMed1994

Mucosal infection of neonatal rhesus monkeys with cell-free SIV.

Although the mechanisms for maternal transmission are unknown, approximately half of the infants congenitally infected with the human immunodeficiency virus type 1 (HIV-1) seem to become infected late in gestation or during delivery. Previously, we have developed a rhesus monkey model for congenital infection by injecting cell-free simian immunodeficiency virus (SIV) directly into amniotic fluid. Our results suggested that fetal infection may have occurred via skin or mucous membrane exposure. Mucosal surfaces have also been implicated as a portal of virus entry by a study in which the presence of serosanguinous fluid in neonatal gastric aspirates correlated with an increased rate of HIV-1 transmission. To test whether cell-free virus could transverse intact neonatal mucosal surfaces, we administered SIVmac251 orally to four rhesus monkey neonates within 1 hr following cesarean section delivery. All four neonates developed viremia and were positive by cocultivation and PCR. Seroconversion occurred in three of the four neonates. The SIV dose given was within physiological range as shown by end-point dilution of virus stock and viremic plasma samples of juvenile rhesus monkeys. This primate model for mucosal transmission of cell-free virus features a high infection rate, thus making studies of mucosal immunity and the development of strategies to prevent intrapartum virus transmission possible.

Animals↗
PubMed1992

Activation of the c-myb locus is insufficient for the rapid induction of disseminated avian B-cell lymphoma.

We have previously reported that infection of 9- to 13-day-old chicken embryos with RAV-1 results in rapid development of a novel B-cell lymphoma in which proviral insertion has activated expression of the c-myb gene (E. Pizer and E. H. Humphries, J. Virol. 63:1630-1640, 1989). The biological properties of these B-cell lymphomas are distinct from those associated with the B-cell lymphomas that develop following avian leukosis virus proviral insertion within the c-myc locus. In an extension of this study, more than 200 chickens, infected as 10- to 11-day-old embryos, were examined for development of lymphomas that possess disrupted c-myb loci. Fourteen percent developed disseminated B-cell lymphoma. In the majority of these tumors, the RAV-1 provirus had inserted between the first and second exons that code for p75c-myb. However, insertions between the second and third exons and between the third and fourth exons were also detected. In situ analysis of myb protein expression in tumor tissue revealed morphological features suggesting that the tumor originates in the bursa. Within the bursa, the lymphoma appeared to spread from follicle to follicle without compromising the structural integrity of the organ. Tumor masses in liver demonstrated heterogeneous levels of myb protein suggestive of biologically distinct subpopulations. In contrast to the morbidity data, immunohistological analysis of bursae from 4- to 6-week-old chickens at risk of developing lymphomas bearing altered c-myb loci revealed lesions expressing elevated levels of myb in 16 of 19 birds. The activated myb lymphoma displayed very poor capacity to proliferate outside its original host. Only 1 of 33 in vivo transfers of tumor to recipient hosts established a transplantable tumor. None of the primary tumor tissue nor the transplantable tumor exhibited the capacity for in vitro proliferation. Similar experimental manipulation has yielded in vitro lines established from avian B-cell lymphomas expressing elevated levels of c-myc or v-rel. The dependence on embryonic infection for development of activated-myb lymphoma suggests a requirement for a specific target cell in which c-myb is activated by proviral insertion. It is likely, moreover, that continued tumor development requires elevated expression of myb proteins within a specific cell population in a restricted stage of differentiation.

Animals↗
PubMed1986

Selective integration of avian leukosis virus in different hematopoietic tissues.

Hematopoietic tissues obtained from avian leukosis virus (ALV)-infected Hyline SC chickens were analyzed for the presence of integrated viral DNA sequences. Cells were prepared from bone marrow, bursa, spleen, thymus, and peripheral blood. Following the removal of erythrocytes, cellular DNAs from each of these tissues were examined by Southern analysis. During the first few weeks of infection, DNA from the bone marrow contained as many as 0.5 copies of viral DNA per haploid genome. Cells from the bursa and peripheral blood contained between 0.05 and 0.15 copies per haploid genome. In contrast, neither splenic nor thymic DNA contained significant levels of viral DNA sequences even though infected birds developed titers of circulating virus between 10(5) and 10(6) IU/ml of plasma. DNA prepared from erythrocytes isolated from the peripheral blood of these birds contained approximately 0.4 copies of integrated viral sequences per haploid genome at 2 weeks after infection. Despite greater levels of integrated sequences in other tissues, by 9 weeks after infection viral sequences were detected only in DNA from bursal lymphocytes. Cells prepared from the spleen and thymus of infected birds were also examined for their size distribution, their internal complexity and their surface expression of immunoglobulin. None of the populations examined differed from normal, uninfected control preparations. These results suggest that ALV infection occurs primarily in the bone marrow and that the different tissues of the hematopoietic system are selectively infected. Further, these results indicate that ALV infection persists longer in bursal lymphocytes than in other hematopoietic tissues. Previous studies have demonstrated that the lymphoid tumors that develop in white leghorn chickens following ALV infection are bursal-dependent B-cell lymphomas that express immunoglobulin M. The observations presented in this communication offer, in part, an explanation for the restricted phenotype of the lymphoid tumor that develops in the SC chicken. Further, the data suggest an explanation for the bursal-dependent nature of the ALV-induced lymphoma.

Animals↗
PubMed1985

Cell lines derived from avian lymphomas exhibit two distinct phenotypes.

Lymphoid cell lines were derived from three avian leukosis virus (ALV)-induced lymphomas. These cell lines contained proviral DNA sequences integrated upstream from the c-myc proto-oncogene, expressed increased levels of c-myc RNA, and were tumorigenic in syngeneic animals. While cell surface immunoglobulin (IgM) was expressed by all three cell lines, only one of the lines secreted IgM into the culture medium. Further, analysis by light microscopy and flow cytometry demonstrated that these cell lines exhibited two distinct morphological and light-scattering profiles. The two nonsecreting lines exhibited a lymphoblastoid phenotype, whereas, the secreting line possessed a more differentiated plasmacytoid phenotype. These findings implicate the activation of c-myc in the pathogenesis of tumors representing two distinct stages of B-cell differentiation within a single animal species.

Animals↗
PubMed1985

Formation of a transformed follicle is necessary but not sufficient for development of an avian leukosis virus-induced lymphoma.

Avian leukosis virus (ALV) infection of susceptible chickens induces bursal lymphomas after a latent period of several months. The clonal development of these B-cell tumors is believed to be a multistep process. Histopathological changes, referred to as transformed follicles, occur within the target organ soon after virus infection and may represent a proximal stage of lymphomagenesis. To establish further the significance of this lesion and its relationship to the subsequent development of lymphomas, we have compared the incidence of transformed follicles observed in animals susceptible or resistant to ALV-induced tumor development. During the 8 weeks following ALV infection, transformed follicles were detected in 82% of the susceptible animals and in 11% of the resistant animals. These results indicate that the incidence of transformed follicles in these animals correlates with their susceptibility to lymphoma development. Furthermore, each transformed follicle does not develop into a tumor. These observations suggest that the formation of a transformed follicle is necessary but not sufficient for lymphoma development.

Animals↗
PubMed1984

Differential response to avian leukosis virus infection exhibited by two chicken lines.

Infection of susceptible chickens with avian leukosis virus (ALV) results in the development of bursal lymphomas. These neoplasms develop within the bursa of Fabricius following a latent period of several months. The response exhibited by two previously uncharacterized chicken lines to ALV infection has been examined. The two lines, Hyline SC and FP, responded differently to ALV infection. During a 24-week period following intravenous ALV infection, 27 of 50 SC chickens developed bursal lymphomas. No lymphomas developed in the 36 FP chickens tested. A majority of the SC chickens that developed lymphomas also exhibited widespread metastasis to the liver, spleen, and kidneys. Analysis of cellular DNA from the primary and metastatic tumors demonstrated the clonal nature of these neoplasms and revealed altered c-myc loci, as reported in other studies, suggesting the importance of this locus in the development of these tumors. Further characterization of the ALV infection of SC and FP chickens will provide an opportunity to analyze the mechanism of resistance and to contribute to the understanding of the tumorigenic process.

Animals↗
PubMed1984

Avian leukosis virus infection: analysis of viremia and DNA integration in susceptible and resistant chicken lines.

Avian leukosis viruses induce lymphoid leukosis, a lymphoma which develops within the bursa of Fabricius several months after virus infection. Chickens from the Hyline SC and FP lines are, respectively, susceptible and resistant to avian leukosis virus-induced lymphoid leukosis. We examined plasma and cellular DNA obtained from avian leukosis virus-infected chickens for the presence of viremia and integrated viral sequences to determine whether the extent of virus infection is comparable in individuals of both lines. A less than twofold difference in the frequency of viremia was detected between chickens of the two different lines. Although the analysis of plasma samples, which were obtained at different times postinfection, demonstrated that the duration of viremia was comparable in both susceptible and resistant chickens, the onset of the viremia observed in susceptible chickens generally preceded by 1 week that observed in resistant chickens. Moreover, integrated viral sequences were detected in approximately 90% of the SC and 40% of the FP chickens. The appearance of infectious virus in the plasma was, in general, associated with the presence of integrated viral sequences in both the bursal cells and the erythrocytes obtained from the same chicken. The presence of both the viremia and the integrated viral DNA sequences was transient, suggesting a mechanism for the elimination of virus-infected cells in both susceptible and resistant chickens. Furthermore, at 5 weeks postinfection no integrated exogenous viral sequences were detected in splenic lymphocytes obtained from either chicken line, regardless of whether these chickens were viremic or had integrated viral sequences detectable in other tissues. Our results indicate that extensive avian leukosis virus replication occurs in approximately 50% of the FP and 100% of the SC chickens. Although it appears that the viral infection spreads more quickly in the SC chickens, our results afford no obvious explanation of the resistance to the development of lymphoma exhibited by FP chickens.

Animals↗