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B Hurtrel

Publications and source records attributed to B Hurtrel.

At least 37 records · Page 2Linked to original sources
PubMed1995

Limited viral spread and rapid immune response in lymph nodes of macaques inoculated with attenuated simian immunodeficiency virus.

A comparative study was undertaken to characterize the very early events that distinguish attenuated and pathogenic simian immunodeficiency virus (SIV) infections. Three rhesus macaques were inoculated with the attenuated SIVmac 251 delta nef virus, and three others with a virus of intermediate phenotype, SIVmac 239 nef stop. They were compared to four macaques inoculated with the pathogenic SIVmac 251 isolate. Lymph nodes (LN) taken between 7 days and 2 months postinoculation were analyzed for SIV expression by in situ hybridization. During acute infection, SIV 21 delta nef infected 1 to 1.5 log10 fewer cells in LN tissue than the pathogenic SIV 251 isolate. The reduction was more marked in the blood, as SIV 251 delta nef infected 2 to 3 log10 fewer PBMC than the isolate and did not yield detectable antigenemia. Morphometric measurements showed that the development of germinal centers (GC) was more rapid in the delta nef infection, which led to a more efficient trapping of viral particles, and could account for antigenemia clearance. The SIV 239 nef stop clone reverted to a nef+ genotype at Week 2, but induced a lower viral burden than a directly pathogenic virus. The kinetics of GC development was rapid, indicating that SIV 239 nef stop induced an immune response similar to that seen in attenuated infection. This study provides evidence that attenuated SIV elicits a more rapid immune response than pathogenic SIV and suggests that an early immunosuppressive episode may facilitate the dissemination of pathogenic SIV.

Amino Acid Sequence↗
PubMed1995

Highly attenuated SIVmac142 is immunogenic but does not protect against SIVmac251 challenge.

We report here the use of the highly attenuated SIVmac142 clone, unable to establish permanent infection of rhesus macaques, in a vaccine trial. Four rhesus macaques were immunized over a long time period with HUT-78 cells infected with wild-type SIVmac142 or, in order to reinforce the safety use of the vaccine, a deleted mutant with similar in vitro infectivity. The first two injections were done with living cells and the remaining boosts with cells emulsified in muramyl dipeptide adjuvant. Three control macaques were injected with uninfected HUT-78 cells. Over 3 years, we have been unable except once to detect viral infections by three methods. However, antibodies directed against the viral Gag proteins and envelope glycoproteins were detected by immunoblots and/or in vitro neutralization assays. All macaques were challenged intravenously with a low dose (10 animal infectious doses) of a highly pathogenic biological clone of SIVmac251 grown on macaque PBMCs. All seven animals became persistently viremic following challenge. The cell-associated viral loads of the vaccinated monkeys were not reduced relative to those of unvaccinated controls during the first weeks postchallenge even if vaccinated monkeys did not present a transient CD4 decrease. Thus, our data reinforced the notion that the efficacy of live attenuated SIV requires the establishment of persistent infection.

Animals↗
PubMed1995

Low susceptibility of resident microglia to simian immunodeficiency virus replication during the early stages of infection.

To assess the susceptibility of resident microglia to simian immunodeficiency virus (SIV) infection, we analysed the brains of rhesus macaques after intracerebral (i.c.) inoculation of the virus into the central region at 7 days, 1, 2 and 3 months post-inoculation (p.i.). The brains of animals showed the same moderate neuropathological changes in central, frontal and parietal regions of the brain, characterized by gliosis, microglial nodules, perivascular infiltrates and occasional white matter pallor and similar low numbers of infected cells detected by in situ hybridization. These results, showing that i.c. inoculation did not lead to preferential infection of brain tissue, even near the inoculation point at 7 days p.i., provide evidence for the low susceptibility of resident microglia to SIV replication during the early stages of infection.

Animals↗
PubMed1995

Permissiveness of Kupffer cells for simian immunodeficiency virus (SIV) and morphological changes in the liver of rhesus monkeys at different periods of SIV infection.

The pathogenesis of liver injury, which remains unclear in the course of human immunodeficiency virus infection, can be investigated in simian immunodeficiency virus-infected macaques, which develop an immunodeficiency disease resembling human acquired immune deficiency syndrome (AIDS). We studied the livers of 21 monkeys infected with simian immunodeficiency virus (SIVmac251) for 4 days to 39 months and detected viral antigens in Kupffer cells, macrophages, and lymphocytes in 65% of the livers tested. Virus-containing cells were present in 5 out of 9 livers tested as early as 4 days postinoculation. The number of positive cells as well as their content in viral proteins substantially increased in sinusoidal cells with the progression of the disease. Morphological features and double immunolabeling indicated that Kupffer cells constituted the predominant cell type containing viral antigens. The presence of multinucleated giant cells displaying the ultrastructural features of resident liver macrophages was another sign of the productive infection of Kupffer cells in vivo, which was attested by the observation of budding, immature, and mature SIV particles. Kupffer cell hyperplasia and hypertrophy were evident and appeared to be related to the development of SIV infection, because a close correlation was found between antigenemia and the surface area occupied by these cells. The Kupffer cells contained apoptotic lymphocytes, indicating that resident liver macrophages could play a role in the uptake of such cells from the blood. The production of tumor necrosis factor alpha (TNF alpha) and, possibly, interferon-alpha by Kupffer cells, the expression of vascular adhesion molecule-1, (VCAM-1), intralobular and periportal inflammation, and the proliferation and expansion of bile duct cells were other signs of liver involvement in SIV infection.

Animals↗
PubMed1994

Programmed cell death and AIDS: significance of T-cell apoptosis in pathogenic and nonpathogenic primate lentiviral infections.

We have proposed that inappropriate induction of programmed cell death (PCD) or apoptosis, a physiological cell-suicide process, may play a role in the pathogenesis of AIDS. This model has been supported by several reports of abnormal levels of PCD in vitro in both CD4+ and CD8+ T cells from human immunodeficiency virus type 1 (HIV-1)-infected persons. To further assess the significance of such a process in AIDS pathogenesis, in vitro PCD was compared in HIV-1-infected persons and in various primate models that allow discrimination between pathogenic chronic lentiviral infection either in the same species, such as rhesus macaques infected with different simian immunodeficiency viruses (SIV), or in different species, such as SIV-infected African green monkeys and HIV-1-infected chimpanzees. Abnormal levels of PCD in CD4(+)-T-cell-depleted peripheral blood mononuclear cells (PBMC), containing the CD8+ T cells, were observed in both pathogenic and nonpathogenic models. However, abnormal levels of PCD in the CD8(+)-T-cell-depleted PBMC, containing the CD4+ T cells, was only observed in the two models leading to AIDS: HIV-1-infected persons and rhesus macaques infected with a pathogenic strain of SIV. This suggests that inappropriate T-cell PCD in HIV-1-infected persons involves two distinct processes: one, concerning CD4+ T cells, is closely related to AIDS pathogenesis; and the other, concerning CD8+ T cells, may be a consequence of immune stimulation with no direct link to AIDS pathogenesis.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Early stages of feline immunodeficiency virus infection in lymph nodes and spleen.

Analysis of the early stages of infection within the lymphoid organs is crucial for the understanding of the physiopathology of HIV infection. Such analysis can only be performed using animal models. Cats were infected with two strains of FIV and killed at regular intervals for a classic pathologic study along with a quantification of the viral load by in situ hybridization in the spleen and the lymph nodes. The pathological study showed a persistent follicular reaction, which peaked 15 days postinoculation (p.i.). The in situ hybridization study showed two types of labeling. The first was spot labeling corresponding to cells actively replicating the virus. The second consisted of a more diffuse labeling linked to the follicular dendritic cells (FDCs) demonstrating by colocalization of virus detected by in situ hybridization associated with the FDCs, specifically labeled by immunohistochemistry. The number of productive cells is few and identical for the two viruses tested. Despite a slight peak at 15 days p.i., the number of infected cells persists while slightly decreasing over time. The FDC virus load appears jointly with the appearance of antibody and remains permanent until the end of the study at 3 years p.i. These results show that in the FIV model, there is a chronic permanent infection in the lymphoid organs. Furthermore, as compared with the SIV-macaque model, there is a correlation between the low number of infected cells detected in these organs in the early phase and the extended length of the asymptomatic period, which contrasts with the high level of the FDC virus load lasting during the same period.

Animals↗
PubMed1994

Variable course of primary simian immunodeficiency virus infection in lymph nodes: relation to disease progression.

To investigate the dynamics of spread of simian immunodeficiency virus (SIV) in the lymphoid organs, we sequentially analyzed the viral burden in lymph nodes (LN) of eight rhesus macaques inoculated intravenously with a high or low dose of the pathogenic SIVmac 251 isolate. For each animal, four axillary or inguinal LN were collected during the first weeks of infection and a fifth LN was taken 6 or 8 months later to estimate disease progression. Measurement of SIV RNA by in situ hybridization showed that all of the macaques studied had a phase of acute viral replication in LN between 7 and 14 days postinoculation which paralleled that observed in the blood. In a second phase, productive infection was controlled and viral particles were trapped in the germinal centers that developed in LN. While the peaks of productive infection were similar for the eight animals, marked differences in the numbers of productively infected cells that persisted in LN after primary infection were seen. Differences were less pronounced in the blood, where productive infection was efficiently controlled in all cases. The persistence of productively infected cells in LN after primary infection was found to be associated with more rapid disease progression, as measured by the decrease of the T4/T8 ratio and the occurrence of clinical signs. However, the persistence of a significant level of viral particles in germinal centers was observed even in animals that remained healthy over a 1- to 2-year observation period. This study indicates that the course of primary SIV infection in LN is variable, and it suggests that the initial capacity of the host to control productive infection in LN may determine the rate of disease progression.

Animals↗
PubMed1994

Early stages of simian immunodeficiency virus infection in lymph nodes. Evidence for high viral load and successive populations of target cells.

Lymph nodes obtained from 14 macaques sacrificed at early time points following experimental inoculation with simian immunodeficiency virus were analyzed by in situ hybridization for virus load and virus cellular tropism. The lymph nodes presented a remarkably high viral load during the early phase of infection, as viral RNA was detected in as many as 2% of lymph node cells 1 week after inoculation. At this stage, macrophages and T4 lymphocytes were identified by combined immunohistochemistry and in situ hybridization as the target cells of the virus. Simian immunodeficiency virus-positive macrophages concentrated in the subcapsular sinuses, suggesting an entry of infected cells via the afferent lymphatics. A shift in the pattern of viral infection was observed at 2 weeks after inoculation, with a concentration of viral RNA in the germinal centers of the developing lymphoid follicles. Follicular dendritic cells were found to be the major target of the virus at this stage. Follicular dendritic cells were associated with high levels of viral RNA but little or no detectable viral DNA, suggesting that the virus was present mostly in the form of viral particles trapped at the cell surface. Follicular dendritic cell-associated virus persisted at high levels for 2 months before subsiding, indicating that follicular dendritic cells constituted a major reservoir of the virus during the early stages of simian immunodeficiency virus infection.

Animals↗
PubMed1993

Structure and variations of feline immunodeficiency virus envelope glycoproteins.

We report the characterization of the env gene of a feline immunodeficiency virus isolate from France (FIV Wo). FIV Wo gag and env genes were cloned directly from cat peripheral blood mononuclear cells, using polymerase chain reaction. The env molecular clone was shown to be functional and to express antigenically relevant envelope glycoproteins in vitro. Alignment of FIV Wo sequences with available FIV sequences and application of a regionalization algorithm resulted in delineation of variable and conserved domains of FIV Env. These data were used to build a schematic folding model of FIV envelope glycoproteins. The Env molecular clone, variability map, and structural model constitute helpful tools for future studies of FIV envelope aimed at the determination of structure-function relationships or design of diagnostics or vaccine reagents.

Animals↗
PubMed1993

Early central nervous system changes in human immunodeficiency virus (HIV)-infection.

Early HIV infection of the CNS, as demonstrated by cerebrospinal fluid studies, seems relatively common. However most HIV carriers remain neurologically unimpaired during the incubation period. A few psychometric, radiological, and electrophysiological studies suggest that neurological abnormalities are present at early stages of HIV infection; the findings of these studies are controversial and until recently, they have not been supported by neuropathological data. Early brain changes, including leptomeningitis and vasculitis with myelin pallor and gliosis of the deep white matter are probably secondary to vascular inflammation and opening of the blood-brain barrier. Such conclusions are drawn from the examination of brains of asymptomatic HIV-positive individuals who died from unnatural causes, and of rare cases with acute fatal encephalopathy revealing HIV infection. In addition, early experimental simian immunodeficiency virus infection and feline immunodeficiency virus encephalopathy have demonstrated similar changes to those in man. Although small amounts of viral genome were detected by PCR in a few cases, the early changes in the human brain do not seem to result from a productive HIV infection of the CNS, as seen in HIV encephalitis. The occurrence of a usually asymptomatic and transient immunopathological reaction coinciding with early HIV infection of the nervous system appears to be more likely.

Animals↗
PubMed1992

Different time course patterns of local expression of delayed-type hypersensitivity to sheep red blood cells in mice.

The delayed-type hypersensitivity (DTH) reaction, a peripheral expression of cell-mediated immunity is still a crucial in vivo immunological test. Nevertheless, the biological significance of its time course remains unclear. Thus, an exhaustive study of DTH was undertaken in mice immunized with increasing doses of sheep red blood cells (SRBC) inoculated intravenously (iv) or subcutaneously. The results showed that overall DTH reactions peaked at 18 hr except in mice iv immunized with the lowest doses (10(5) and 10(6)) and elicited at Day 4. The protracted DTH reaction was shown to be associated with an histological picture of tuberculin-type reaction. A part of the 18-hr DTH reaction is mediated by serum in mice inoculated with large doses of SRBC; nevertheless, numeration by limiting dilution analysis of circulating DTH cells showed that the frequency of these cells correlates with the 18-hr DTH level. The protracted DTH shown at 42 and 48 hr, 4 days after immunization with 10(5) and 10(6) SRBC, could not be transferred in naive recipients with immune spleen cells; it was independent of the antigen life span and did not result from immunization modulation at the bone marrow level on recruitable cells.

Animals↗
PubMed1992

Comparison of early and late feline immunodeficiency virus encephalopathies.

DESIGN: The study of the early and late stages of encephalopathy following infection by the feline immunodeficiency virus (FIV) was carried out with laboratory and naturally infected cats. INTERVENTIONS: Animals infected experimentally were injected with three different isolates of the virus, administered either intracerebrally or intravenously, and sacrificed at 7 days, 1 and 6 months (intracerebral injection), and 2, 6 and 12 months (intravenous injection) post-inoculation, respectively. CONCLUSIONS: General features of encephalopathy were found to be identical, regardless of the method of inoculation or the viral strain used. Moderate gliosis and glial nodules, sometimes associated with perivascular infiltrates and white matter pallor, were observed at 1 month (intracerebral injection) and 2 months (intravenous injection), and remained unchanged until 12 months post-inoculation. The fact that these initial stages are identical for intravenously and intracerebrally inoculated cats suggests that the virus enters the brain very quickly in intravenously infected animals. Encephalopathy in cats naturally infected with FIV only consisted of gliosis, glial nodules, white matter pallor, meningeal perivascular calcification and meningitis. These lesions were more frequent and more severe in the group coinfected with feline leukaemia virus and feline infectious peritonitis virus. Although multinucleated cells were rare, the strong similarities between HIV and simian immunodeficiency virus encephalopathies at comparable stages support the view that FIV infection may represent an interesting model for a physiopathological approach of HIV infection of the central nervous system.

Animals↗
PubMed1991

Early viral replication in the brain of SIV-infected rhesus monkeys.

To investigate the mechanism of simian immunodeficiency virus (SIV) entry into the central nervous system (CNS) and the initial events leading to neuropathogenesis, SIV replication was studied by in situ hybridization in the CNS of 5 Rhesus macaques at 7 days, 1, 2, and 3 months after SIV intravenous inoculation. CNS infection was found to be a frequent and early event, as SIV was detected in the CNS of all the animals studied and as early as 7 days postinoculation. At the earliest stage, the infection localized mainly to perivascular cells. Using combined immunohistochemistry and in situ hybridization, infected cells were shown to express the CD68 marker, suggesting that infected mononuclear phagocytes crossing the blood-brain barrier represent the main source of virus in the CNS. Early viral replication coincided with neuropathologic changes, consisting in gliosis, perivascular infiltrates and rare glial nodules. Immunophenotyping of brain tissue showed that increased macrophage infiltration, microglial reactivity and MHC class II induction occurred within the first week of infection, indicating a possible immunopathologic mechanism in early CNS pathogenesis.

Animals↗
PubMed1991

Early SIV encephalopathy.

SIV encephalopathy was studied in rhesus macaques early after intracerebral (IC) or intravenous (IV) inoculation. Although SIV was detected in the brain of all IC-inoculated animals, the CNS showed moderate neuropathological changes. IV-inoculated animals presented a spectrum of brain changes ranging from perivascular infiltrates to multinucleated giant cells. CNS infection was detected as early as seven days post-IV-inoculation, mostly in a perivascular localization. Using combined immunohistochemistry and in situ hybridization, infected cells were shown to express macrophage markers.

AIDS Dementia Complex↗
PubMed1986

[Action of immunostimulants on phagocytosis and derivative actions].

One of the main objectives of immunopotentiators is their ability to enhance or to restore natural anti-infectious resistance of normal or immunocompromised hosts. Numerous experimental resistance models have been used in screening such potentiators. However, once such a substance has been selected, its potential and practical use will directly depend on the knowledge of the underlying resistance mechanisms induced, defining its cellular or molecular targets. Phagocytosis-polymorphonuclear or monocyte-macrophage dependent--is the most frequently described variable which have been analysed among the various potentially active mechanisms of non-specific resistance. Various in vivo and in vitro tests might be used and the target of several immunostimulants among the different steps of phagocytosis are described. However, numerous intrinsic limitations are associated with such tests and news models or tests are presented and discussed in order to gain more insights into the evaluation of active substances.

Adjuvants, Immunologic↗
PubMed1986

Various strains of BCG vaccine and genetic control of the immune response of mice.

Numerous field trials of BCG vaccine, undertaken to evaluate its effectiveness in the prophylaxis of human tuberculosis, indicated that the levels of protection achieved were not uniform. Most probable factors influencing these results are: partial protection due to atypical mycobacteria, tuberculosis expectancy in different population, nutritional and socio-economic factors, potency of BCG vaccines, and genetic factors controlling the host immune response. Specific and non specific hallmarks of cell-mediated immunity after BCG infection were analysed in various outbred, inbred and recombinant lines of mice, testing the capacity of different preparations and strains of BCG vaccine. Results of such studies did show that the by far most important factor involved the type of immune response related to gene(s) controlling the natural resistance and the expression of C.M.I. Consequences for future mass and individual BCG vaccination as well as the proper integration of BCG vaccination in antituberculous policy are discussed.

Animals↗