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1.
A virulent strain of eastern equine encephalomyelitis virus produced in hamsters a lethal infection with severe lesions of nerve cells predominatly in the anterior parts of the brain. Parenchyma necroses occurred in the liver and lymphoid organs. Infectious virus and viral antigen were found in all the organs examined with the greatest accumulation in the brain. Attenuated variants of the virus produced in most hamsters an inapparent infection. In some animals without clinical signs, focal inflammatory-dystrophic lesions were found in the central nervous system (CNS) and the liver, as were immunomorphological changes in the lymphoid tissue. In the latter infectious virus could be detected for 6 days after inoculation (p.i.), whereas in the brain only viral antigen could be found up to 14 days. At 3 and 6 months p.i., no persistence of attenuated virus in the brain and lymphoid tissues could be established by organ culture and co-cultivation methods. Nor was virus antigen detected. No pathomorphological changes or proliferative-hypertrophic astrocyte reaction were found. 相似文献
2.
Pathogenesis of Rinderpest Virus Infection in Rabbits II. Effect of Rinderpest Virus on the Immune Functions of Rabbits
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Kazuya Yamanouchi Akiko Fukuda Fumio Kobune Yasuhiro Yoshikawa Fumitoshi Chino 《Infection and immunity》1974,9(2):206-211
Rinderpest virus infection was shown to induce marked suppression of both humoral antibody response and cell-mediated immunity in rabbits. The virus exhibited a suppressive effect on primary antibody response as indicated by a decrease in numbers of plaque-forming cells (immunoglobulin [Ig]M) and hemagglutinating antibody titers of both IgM and IgG types to sheep red blood cells, whereas there was no detectable effect of the virus on the production of memory cells. Virus-induced suppression of cell-mediated immunity was demonstrated by a decreased rate of proliferative response of peripheral lymphocytes to phytohemagglutinin stimulus and by a depression of delayed-type skin reactions to purified protein derivative. Such suppressive effects were indicated to persist for 14 days or longer. Alteration in phagocytic activity of the reticuloendothelial system was not observed. The relevance of the virus-induced histological lesions in the lymphoid tissues to the virus-induced immunosuppression was discussed. 相似文献
3.
Induction of Mucosal B-Cell Memory by Intranasal Immunization of Mice with Respiratory Syncytial Virus 总被引:1,自引:0,他引:1
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Janine Valosky Haruka Hishiki Theoklis E. Zaoutis Susan E. Coffin 《Clinical and Vaccine Immunology : CVI》2005,12(1):171-179
The capacity of live or inactivated respiratory syncytial virus (RSV) to induce B-cell memory in respiratory-associated lymphoid tissues of mice was examined. Eight weeks after primary inoculation with either live or inactivated RSV, adult BALB/c mice were challenged with 4 × 105 PFU of RSV. Protection from viral shedding and mucosal production of RSV-specific antibodies were examined at various time points after challenge. We found that primary immunization with live, but not inactivated, RSV induced complete and durable protection upon challenge within the upper and lower respiratory tract. Also, primary immunization with live, but not inactivated, RSV enhanced the production of mucosal RSV-specific immunoglobulin A (IgA) upon challenge. Secondary mucosal IgA responses were characterized by (i) the early production of mucosal IgA by B cells that reside in organized nasal-associated lymphoid tissues, cervical lymph nodes, and bronchial lymph nodes, and (ii) the subsequent production of RSV-specific IgA by mucosal effector tissues, such as the tracheal lamina propria and lung. These findings suggest that primary infection of mice with live RSV might induce mucosal IgA-committed memory B cells. A greater understanding of the characteristics of RSA-specific mucosal memory B cells may facilitate the development of an RSV vaccine. 相似文献
4.
Host Defense Mechanisms Against Herpes Simplex Virus I. Control of Infection In Vitro by Sensitized Spleen Cells and Antibody
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Francis A. Ennis 《Infection and immunity》1973,7(6):898-904
Sensitized mouse spleen cells decrease the spread of herpes simplex virus infection in cell culture lines derived from human and murine tissues. These washed, sensitized cells act alone and additively in combination with antibody to diminish the ability of single virus-infected cells to spread infection to contiguous cells. This control of infection is not species specific, unlike interferon, and appears to be distinct from the effect of antibody. Lymphotoxin was not detected in this lymphocyte-mediated response. This control of herpes simplex virus infection in vitro by sensitized lymphoid cells is immunologically specific; spleen cells from donor animals immunized with a heterotypic virus do not cause herpesvirus plaque size reduction. The ratio of spleen cells from immunized animals to target monolayer cells needed to produce this effect is > 4:1. Plaque size reduction of herpes simplex virus by spleen cells requires intact, immune, non-glass-adhering lymphoid cells. 相似文献
5.
Duck virus enteritis is an acute and contagious herpesvirus infection of duck, geese and swans with high morbidity and mortality. The kinetics of viral DNA loads and immunohistochemical localization of virulent duck enteritis virus, as well as histopathological examination in various tissues of ducks following oral infection, were investigated. The time course for the appearance of viral antigen and tissue lesions in various tissues was coincident with the levels of duck enteritis virus at the various sites, suggesting that the levels of duck enteritis virus in systemic organs have a close correlation with the progression of disease. The abundance of target epithelial and lymphoid cells may contribute to the high levels of virus infection and replication in lymphoid and intestinal tissues. 相似文献
6.
The effects of cytomegalovirus (CMV) infection on hematopoietic and lymphoid tissues were studied in guinea pigs. Blood parameters, histopathology, and virus distribution in the bone marrow, spleen, lymph nodes, and thymus were assessed during primary nonlethal acute and chronic guinea pig CMV infection. Transient hematological changes comparable to those seen in human CMV mononucleosis were observed during acute infection. These included anemia and leukocytosis with atypical lymphocytes. Splenomegaly and stimulation of spleen and lymph node T- and B-cell areas were also noted. These changes occurred at the peak of virus recovery from all tissues tested, as well as from macrophages and B- and T- cell-enriched spleen subpopulations. Virus was cleared rapidly from blood and bone marrow; blood counts, spleen size, and histology returned to normal within 1 month after virus inoculation. However, guinea pigs failed to eliminate the virus completely from lymphoid tissues, since virus persisted in splenic macrophage and B-lymphocyte-enriched populations during chronic infection. The data suggest that CMV-infected mononuclear cells play a role in the establishment of generalized acute infection and virus persistence. 相似文献
7.
Moniuszko M Bogdan D Pal R Venzon D Stevceva L Nacsa J Tryniszewska E Edghill-Smith Y Wolinsky SM Franchini G 《Virology》2005,333(1):159-168
Plasma virus in human immunodeficiency virus type 1/simian immunodeficiency virus (HIV-1/SIV) infection most likely results from the combination of viruses produced in different tissues. As immunological pressure may be higher in effector sites than secondary lymphoid tissues, we investigated quantitative and qualitative changes in viral RNA in blood and tissues of 10 Mamu-A*01-positive SIV-infected macaques in parallel with the frequency of CD8+ T cells recognizing the dominant Gag181-189 CM9 epitope. The plasma virus level in these macaques directly correlated with the viral RNA levels in lymph nodes, spleen, lungs, colon, and jejunum. In contrast, the frequency of the Gag181-189 CM9 tetramer did not correlate with SIV RNA levels in any compartment. We investigated the presence of viral immune escape in RNA from several tissues. The complete substitution of wild-type genotype with viral immune-escape variant within the Gag181-189 CM9 epitope was associated with low tetramer response in all tissues and blood of two macaques. In one macaque, the replacement of wild type with an immune-escape mutant was asynchronous. While the mutant virus was prevalent in blood and effector tissues (lungs, jejunum, and colon), secondary lymphoid organs such as spleen and lymph nodes still retained 80% and 40%, respectively, of the wild-type virus. These results may imply that there are differences in the immunological pressure exerted by cytotoxic T lymphocytes (CTLs) in tissue compartments of SIVmac251-infected macaques. 相似文献
8.
S Prevot J Audouin J Andre-Bougaran R Griffais A Le Tourneau J G Fournier J Diebold 《American journal of clinical pathology》1992,97(3):420-425
An enlargement of the thymus suggesting a tumor was discovered in a 28-year-old man who had early-stage acquired immune deficiency syndrome. A biopsy was performed. The adipose involuted thymus, with persistence of many Hassall's corpuscles, was judged to be a large lymphoid follicular hyperplasia. This follicular hyperplasia was similar to that previously described for lymph nodes, spleen, and other lymphoid tissues at earlier stages of human immunodeficiency virus infection, before the development of acquired immune deficiency syndrome. Human immunodeficiency virus RNA and p24 human immunodeficiency virus protein were detected in the hyperplastic germinal centers (lymphocytes and follicular dendritic infected cells), and also in many cells that may have been either lymphocytes and/or epithelial cells in the interfollicular areas. The tissue was negative for Epstein-Barr virus DNA sequences, as determined by the polymerase chain reaction. These observations identify the first state of infection of the thymus in a human immune deficiency virus-infected adult, preceding the severe involution with lymphoid depletion observed in all fatal cases of acquired immunodeficiency syndrome in which the thymus has been analyzed. 相似文献
9.
J W Said P N Stoll P Shintaku J M Bindl J R Butmarc G S Pinkus 《American journal of clinical pathology》1989,91(5):542-549
Monoclonal antibody Leu-22 represents an effective reagent for detection of neoplastic and nonneoplastic T-cells in paraffin sections of routinely processed tissues (242 specimens evaluated). In nonneoplastic tissues, immunoreactivity was localized mainly to lymphoid cells corresponding to a T-cell distribution. Immunoreactivity in lymphoid neoplasms, however, was preferentially, but not exclusively, limited to T-cell populations. Fifty-four of 60 T-cell neoplasms (90%) of various histologic types were Leu-22 positive. The pattern of immunoreactivity consisted mainly of membrane staining, with focal weak cytoplasmic positivity. Twenty-five of 67 B-cell neoplasms (37%) were also Leu-22 positive, with low-grade lymphomas (well/moderately well-differentiated lymphocytic types) representing most immunoreactive cases. In Hodgkin's disease, although most small lymphoid cells were Leu-22 positive, only rare Reed-Sternberg cells were immunoreactive. In all cases, histiocytes and myeloid cells exhibited variable immunoreactivity. The epitope identified by Leu-22 was detectable in formalin- and B5-fixed tissues but apparently was denatured after fixation in Zenker's-acetic acid solution used for bone marrow biopsies. Evaluation of a wide variety of nonhematopoietic neoplasms (64 total) revealed diffuse cytoplasmic staining in a few cases. However, membrane staining, typically noted for lymphoid cells, was not observed. Leu-22 potentially represents a useful marker for lymphoid cells, preferentially of T-cell origin, with optimal applicability as part of a panel that includes an effective pan-B-cell marker. 相似文献
10.
The lymphoid tissues of 9 monkeys infected experimentally with wild type measles virus were examined by light and electron microscopy. Multinucleated giant cells of the Warthin-Finkeldey type were found 7 to 11 days after virus inoculation. The giant cells occurred mostly in the germinal center of lymphatic follicles, where they underwent degeneration and disappeared rapidly. Lymphoid and reticular types of giant cells were recognized. The ultrastructural evidence suggested that some of the nuclei contained in giant cells were formed by an aberrant nuclear cleavage. The majority of giant cells, however, were postulated to arise from virus-mediated cell fusion, although direct evidence of cell fusion was not seen. Peculiar nuclear changes, in which some nuclei and fragments of the outer nuclear membrane were contained in a common outer membrane of the nuclear envelope, were observed in all lymphoid giant cells. Both cytoplasmic and intranuclear inclusions were seen to be composed of viral nucleoprotein strands. The former were detected in all giant cells of both types, and the latter in occasional nuclei, providing the direct evidence that giant cell formation resulted from replication of the virus. 相似文献
11.
Early events in tissues during infection with pathogenic (SIVmac239) and nonpathogenic (SIVmac1A11) molecular clones of simian immunodeficiency virus. 总被引:12,自引:11,他引:12
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A. A. Lackner P. Vogel R. A. Ramos J. D. Kluge M. Marthas 《The American journal of pathology》1994,145(2):428-439
The extent of virus replication, tissue distribution, localization of virus within tissues, and the presence of pathological lesions was examined early after experimental infection of rhesus monkeys with simian immunodeficiency virus (SIV). Three strains of SIV were used: molecularly cloned pathogenic SIVmac239; molecularly cloned nonpathogenic SIVmac1A11; and uncloned pathogenic SIVmac. The major targets of infection in all animals at 2 weeks postinoculation were the thymus and spleen. The distribution of virus within lymphoid organs varied with the viral inoculum: nonpathogenic SIVmac1A11 was present primarily within lymphoid follicles and in the thymic cortex; SIVmac239 was present primarily within periarteriolar lymphoid sheaths in the spleen, the paracortex of lymph nodes, and the medulla of the thymus; uncloned SIVmac was present in all these areas but tended to parallel the distribution of SIVmac239. Animals inoculated with nonpathogenic SIVmac1A11 had fewer SIV-positive cells by in situ hybridization and after 13 weeks postinoculation, virus was undetectable in any tissue from these animals. No significant pathological abnormalities were recognized in animals inoculated with this nonpathogenic virus. In contrast, nearly half of the animals inoculated with either SIVmac or SIVmac239 developed significant pathological lesions, including opportunistic infections by 13 weeks postinoculation, highlighting the virulence of these viruses. Our results indicate marked differences in tissue distribution between pathogenic and nonpathogenic molecular clones of SIV during the acute phase of infection. The most striking differences were the absence of SIVmac1A11 from the central nervous system and thymic medulla. The prominent early involvement of the thymus suggests that infection of this organ is a key event in the induction of immune suppression by SIV. 相似文献
12.
The pathology of experimental aerosolized monkeypox virus infection in cynomolgus monkeys (Macaca fascicularis). 总被引:5,自引:0,他引:5
G M Zaucha P B Jahrling T W Geisbert J R Swearengen L Hensley 《Laboratory investigation; a journal of technical methods and pathology》2001,81(12):1581-1600
Cynomolgus monkeys (Macaca fascicularis) were exposed by fine-particle aerosol to lethal doses of monkeypox virus, Zaire strain. Death, attributable to fibrinonecrotic bronchopneumonia, occurred 9 to 17 days postexposure. Lower airway epithelium served as the principal target for primary infection. The relative degree of involvement among lymphoid tissues suggested that tonsil, mediastinal, and mandibular lymph nodes were also infected early in the course of the disease, and may have served as additional, although subordinate, sites of primary replication. The distribution of lesions was consistent with lymphatogenous spread to the mediastinal lymph nodes and systemic dissemination of the virus through a monocytic cell-associated viremia. This resulted in lesions affecting other lymph nodes, the thymus, spleen, skin, oral mucosa, gastrointestinal tract, and reproductive system. The mononuclear phagocyte/dendritic cell system was the principal target within lymphoid tissues and may also have provided the means of entry into other systemic sites. Hepatic involvement was uncommon. Lesions at all affected sites were characterized morphologically as necrotizing. Terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate nick-end labeling (TUNEL) staining of select lesions suggested that cell death within lymphoid and epithelial tissues was due in large part to apoptosis. Skin and mucosal surfaces of the respiratory and gastrointestinal tracts also exhibited variable proliferation of epithelial cells and subjacent fibroblasts. Epithelial intracytoplasmic inclusion bodies, consistent with Guarnieri bodies, were usually inconspicuous by light microscopy, but when present, were most readily apparent in the stratified squamous epithelium of the oral mucosa and epidermis. Multinucleated syncytial cells were also occasionally observed in the stratified squamous epithelium of the tongue, tonsil, and skin, and in the intestinal mucosa. Monkeypox virus antigen was readily demonstrated by immunohistochemistry using anti-vaccinia mouse polyclonal antibodies as well as anti-monkeypox rabbit polyclonal antibodies. Detectable poxviral antigen was limited to sites exhibiting obvious morphologic involvement and was most prominent within epithelial cells, macrophages, dendritic cells, and fibroblasts of affected tissues. The presence of poxviral antigen, as determined by immunohistochemistry, correlated with ultrastructural identification of replicating virus. Concurrent bacterial septicemia, present in one monkey, was associated with increased dissemination of the virus to the liver, spleen, and bone marrow and resulted in a more rapidly fatal clinical course. 相似文献
13.
Lymphatic tissues (spleen, mesenteric lymph nodes, thymus) from 24 cats with spontaneous feline infectious peritonitis (FIP) were examined by light microscopy and immunohistochemistry for cellularity, cellular composition, and degree of cellular turnover. Additionally, the formation of granulomatous lesions in lymphatic tissues in cats with FIP was examined. For comparison, tissues from 14 specific pathogen-free (SPF) cats and seven cats infected with FIP virus (FIPV; as the result of long-term exposure) but free from FIP were examined. In cats with FIP, the precardial mediastinum (including site of the thymus) and mesenteric lymph node parenchyma were often affected by granulomatous-necrotizing processes. In general, lymphoid tissues showed T- and B-cell depletion, often including massive to complete thymic involution or atrophy. In some cases, the number of apoptotic lymphocytes was increased in lymphoid follicles as well as in T-cell zones. The number of macrophages was increased in the splenic red pulp. In contrast, the FIPV-exposed cats without FIP generally showed a distinct lymphoid hyperplasia. The findings indicated that the major difference in lymphatic tissues between FIPV-infected cats with FIP and those without FIP was the development of lymphocyte depletion in the first group and lymphocyte proliferation in the second. 相似文献
14.
Fascin,a sensitive new marker for Reed-Sternberg cells of hodgkin's disease. Evidence for a dendritic or B cell derivation?
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G. S. Pinkus J. L. Pinkus E. Langhoff F. Matsumura S. Yamashiro G. Mosialos J. W. Said 《The American journal of pathology》1997,150(2):543-562
Immunohistochemical localization of human fascin, a distinct 55-kd actin-bundling protein, was determined for a wide variety of lymphoid tissues (364 specimens total). In non-neoplastic tissues, reactivity was highly selective and localized predominantly in dendritic cells. In the thymus, this protein was distinctly localized to medullary dendritic cells. In reactive nodes, interdigitating reticulum cells of T zones, cells in subcapsular areas, and cells of the reticular network were reactive, with variable reactivity observed for follicular dendritic cells. Splenic dendritic cells of the white pulp and sinus-lining cells of the red pulp were reactive. Endothelial cells of all tissues exhibited variable reactivity. Lymphoid cells, myeloid cells, and plasma cells were uniformly nonreactive. In the peripheral blood, only dendritic (veiled) cells were reactive for fascin. A striking finding was observed for cases of Hodgkin''s disease (total 187 cases). In all cases of nodular sclerosis (132), mixed cellularity (34), lymphocyte depletion (2), and unclassified types (5), all or nearly all Reed-Sternberg cells and variants were immunoreactive for fascin. Neoplastic cells exhibited strong diffuse cytoplasmic staining and frequently assumed dendritic shapes, particularly in the nodular sclerosis type, producing an interdigitating meshwork or syncytial network of cells. In cases of mixed cellularity type, neoplastic cells generally appeared more discrete. In all 14 cases of nodular lymphocyte predominance type, L&H variants were nonreactive. By contrast, neoplastic lymphoid cells of only 24 of 156 (15%) other lymphoid neoplasms (127 B cell, 27 T cell, and two null cell evaluated) were reactive for fascin. Fascin represents a highly effective marker for detection of certain dendritic cells in normal and neoplastic tissues, is an extremely consistent marker for Reed-Sternberg cells and variants of Hodgkin''s disease (except L&H types), and may be helpful to distinguish between Hodgkin''s disease and non-Hodgkin''s lymphoma in difficult cases. The staining profile for fascin raises the possibility of a dendritic cell derivation, particularly an interdigitating reticulum cell, for the neoplastic cells of Hodgkin''s disease, notably in nodular sclerosis type. However, as fascin expression may be induced by Epstein-Barr virus infection of B cells, the possibility that viral induction of fascin in lymphoid or other cell types must also be considered in Epstein-Barr virus-positive cases. 相似文献
15.
An animal model was designed for use in studies of initial cellular immune responses to virus infection of the intestinal mucosa. The animal chosen was the New Zealand White rabbit and the mucosal site the subterminal ileum, isolated in a Thirty-Vella loop. The antigen used was parainfluenzavirus type 3, which would normally be destroyed by bile salts if ingested. Loops approximately 20 cm in length, each containing at least one Peyer's patch, were exteriorised through left paramedian stomata. Atrophic changes began to appear in the loops by 7 days, but no observable diminution in their associated lymphoid tissues was evident. The genesis of parainfluenzavirus type 3 infection in the loops was monitored by assay of sequential loop washings for infectious virus and in fluorescent antibody studies of cells from infected loop epithelia. Infectious virus was recovered for up to 13 days after inoculation and specific intracytoplasmic immunofluorescence was detected in loop epithelial cells. There was little serological evidence of systemic spread of the virus. A localised cellular immune response against parainfluenzavirus type 3 was mounted in the lymphoid tissues associated with the infected loops by day 14, but was not detected in systemic lymphoid tissues. No reactivity was detected in rabbits given inactivated virus via their loops or in those receiving infectious virus intravenously. This model appears to be capable of generating mucosal cellular responses to infection and may therefore be suitable for further studies in this field. 相似文献
16.
The development of the lymphoid tissues of a model marsupial, the stripe-faced dunnart, has been described from birth to weaning, a period of 2.5 months. At birth the lymphoid tissues, including the thymus, lymph nodes and mucosa-associated lymphoid tissues, were undeveloped. A thoracic thymus consisting primarily of stromal tissue was observed by day 4 after birth but by day 12, lymphocytes were observed in the thymus and some cortico-medullary differentiation was apparent. Lymph nodes were histologically mature by day 31, the earliest day investigated for this tissue. In gut tissue, lymphoid follicles were first observed by day 57 post-partum. No bronchus-associated lymphoid tissue was observed in any lung samples. The thymus, lymph nodes and gut-associated lymphoid tissues were all distinguishable before weaning (day 70) but not all were histologically mature. The sequence of development of the lymphoid tissues in the stripe-faced dunnart was similar to those observed in other marsupial species. 相似文献
17.
B Madea H J Roewert G R Krueger D V Ablashi S F Josephs 《Archives of pathology & laboratory medicine》1990,114(4):379-382
Histologic studies supplemented by in situ hybridization for human immunodeficiency virus type 1 (HIV-1), Epstein-Barr virus, cytomegalovirus, and human herpesvirus type 6 were performed on tissues obtained from the autopsy of six patients who died either by homicide or suicide shortly after learning of their seroconversion. Except for mild nonspecific lymphoid tissue reactions, no lesions were noted that would indicate HIV-1 infection. DNA from all viruses was detected in some lymphoid cells. The amount of DNA for Epstein-Barr virus, cytomegalovirus, and human herpesvirus type 6 corresponded to that observed for clinically occult latent infection. Lymphoid cells carrying HIV-1 DNA were even less frequent. Cells positive for HIV-1 were noted in the lamina propria of the large intestine in three male homosexuals and in one female prostitute. The cells were arranged similar to antigen-presenting cells. The present findings are consistent with current theories regarding the pathogenesis of HIV-1-associated disease. 相似文献
18.
Summary. BALB/c mice were inoculated with 3 EHV-2 low passage isolates. After intranasal inoculation, viral DNA was detected by virus-specific
nested PCR in the lung up to day 30 post inoculation and in nasal turbinates till day 7. In trigeminal ganglia, olfactory
bulb, brain and lymph nodes viral DNA was randomly shown by PCR. After intraperitoneal inoculation viral DNA was present in
lymphoid tissues. The spleen was PCR positive up to day 30 and showed a splenomegaly. Clinical signs, virus replication and
viraemia, were not observed and no virus strain-specific differences were obvious. Control mice inoculated with equine herpesvirus
4 were PCR negative in all tissues.
Received November 5, 2001; accepted March 13, 2002 Published online May 24, 2002 相似文献
19.
Pathogenesis of visna. I. Sequential virologic, serologic, and pathologic studies. 总被引:19,自引:0,他引:19
G Pétursson N Nathanson G Georgsson H Panitch P A Pálsson 《Laboratory investigation; a journal of technical methods and pathology》1976,35(4):402-412
A total of 56 Icelandic sheep were infected with visna virus by intracerebral injection of strain 1514 and the course of infection was followed for 12 months. Virus was isolated from more than 90 per cent of the animals, primarily from central nervous system and lymphoid tissues. However, titers of free infectious virus were minimal and virus isolation often required the use of tissue explants. All sheep raised serum-neutralizing and complement-fixing antibodies beginning 1 to 3 months after infection. Differences in neutralization titers against the infecting strain (1514) and a reference strain (796) suggested that antigenic drift might occur during prolonged infection. High cerebrospinal fluid neutralization titers in the spinal fluid indicated local antibody production in the central nervous system. Although the incidence of clinical disease during the 1st year of infection was less that 10 per cent, approximately 80 per cent of the sheep examined had central nervous system histologic lesions of variable severity, which were marked 1 month after infection with little progression during the subsequent year. There was a striking correlation between the severity of central nervous system lesions and the frequency of virus isolations from all tissues. These observations provide detailed base line data on visna infection, suggest some of the mechanisms responsible for the persistence of infection and for the slowness and irregularity of disease occurrence, and form the basis for further experiments on the role of immunologic mechanisms in the pathogenesis of this slow infection. 相似文献
20.
Kinman L Bui T Larsen K Tsai CC Anderson D Morton WR Hu SL Ho RJ 《Journal of acquired immune deficiency syndromes (1999)》2006,42(2):155-161
In HIV-infected persons on highly active antiretroviral therapy, residual virus is found in lymphoid tissues. Indinavir concentrations in lymph node mononuclear cells of patients on highly active antiretroviral therapy were approximately 25% to 35% of those in blood mononuclear cells, suggesting that drug insufficiency contributes to residual virus in lymphoid tissues. Therefore, we developed novel lipid-indinavir nanoparticles targeted to lymphoid tissues. Given subcutaneously, these nanoparticles provided indinavir concentrations 250% to 2270% higher than plasma indinavir concentrations in both peripheral and visceral lymph nodes. Improved indinavir delivery was reflected in reduced viral RNA and CD4(+) T-cell rebound. This study optimized lipid nanoparticle formulation with respect to indinavir in lymphoid tissues of HIV-infected macaques. Regardless of lipid characteristic tested (charge, fluidity, and steric modification), indinavir binds completely to lipid at pH 7.4 but is reversed at pH 5.5 or lower. Compared with previous formulations, nanoparticles composed of disteroyl phosphatidylcholine and methyl polyethylene glycol-disteroyl phosphatidylethanolamine (DSPC:mPEG-DSPE) provided 6-fold higher indinavir levels in lymph nodes and enhanced drug exposure in blood. Enhanced anti-HIV activity paralleled improved intracellular drug accumulation. Collectively, these data suggest that indinavir nanoparticles composed of DSPC:mPEG-DSPE provided the most effective lymphoid delivery and could maximally suppress the virus in lymphoid tissues. 相似文献