RESUMO
A type D retrovirus related to but distinct from Mason-Pfizer monkey virus was isolated in vitro from the blood of two rhesus monkeys (Macaca mulatta) with simian acquired immunodeficiency syndrome (SAIDS). Three juvenile rhesus monkeys that were injected intravenously with tissue culture fluids containing this virus developed SAIDS after 2 to 4 weeks.
Assuntos
Síndrome da Imunodeficiência Adquirida/veterinária , Macaca mulatta/microbiologia , Macaca/microbiologia , Retroviridae/isolamento & purificação , Síndrome da Imunodeficiência Adquirida/microbiologia , Síndrome da Imunodeficiência Adquirida/transmissão , Animais , Antígenos Virais/imunologia , Modelos Animais de Doenças , Feminino , Masculino , Retroviridae/imunologia , Retroviridae/ultraestrutura , Proteínas do Core Viral , Proteínas do Envelope Viral/imunologia , Proteínas Virais/imunologiaRESUMO
Simian acquired immunodeficiency syndrome (SAIDS), a disease clinically and pathologically similar to acquired immunodeficiency syndrome in humans, was transmitted from diseased rhesus monkeys (Macaca mulatta) to normal monkeys by inoculation with heparinized whole blood or plasma that had been passed through filters of 0.45 micrometer pore size. This suggests that the causative agent is small and most probably a virus. No viruses, however, were isolated by standard cell culture techniques from the blood or filtered plasma which caused SAIDS. Both cellular and humoral immunity were markedly depressed in animals with advanced SAIDS.
Assuntos
Síndrome da Imunodeficiência Adquirida/transmissão , Plasma , Síndrome da Imunodeficiência Adquirida/sangue , Síndrome da Imunodeficiência Adquirida/imunologia , Animais , Sangue/microbiologia , Citomegalovirus/isolamento & purificação , Filtração , Imunoglobulinas/análise , Sistema Linfático/patologia , Ativação Linfocitária , Macaca mulatta , Plasma/microbiologia , Retroviridae/isolamento & purificação , Vírus/isolamento & purificaçãoRESUMO
A 2.5-year epidemiologic study of a breeding group of rhesus monkeys (Macaca mulatta), which is a focus of endemic simian acquired immunodeficiency syndrome (SAIDS), demonstrated a strong association between the occurrence of SAIDS and infection with a type D retrovirus, SAIDS retrovirus serotype 1 (SRV-1). Of 23 healthy "tracer" juvenile rhesus monkeys, 19 (83%) died with SAIDS within 9 months of introduction into the resident SAIDS-endemic population. In contrast, 21 healthy "sentinel" juvenile rhesus monkeys placed in the same outdoor enclosure but denied physical contact with the SAIDS-affected group by a 10-foot-wide "buffer zone" remained free of SRV-1, SRV-1 antibody, and disease for 2.5 years. The SAIDS-specific mortality rate was significantly higher in juveniles than in adults. In repeated serologic testing, the overall prevalence of SRV-1 antibody ranged from 68 to 85%. Antibody prevalence increased with age. Seroconversion was found to be a poor indicator of infection rate, as approximately 50% of virus-positive juvenile monkeys had no antibody detectable by enzyme-linked immunosorbent assay. Repeated viral isolations from all animals revealed 1) SRV-1 viremia with clinical SAIDS; 2) persistent viremia and viral shedding in apparently healthy animals; 3) transient viremia and clinical recovery; 4) intermittent viremia, suggesting activation of latent infections; and 5) viremia in a 1-day-old infant, suggesting transplacental transmission. The prevalence of SRV-1 antibody in SAIDS-free breeding groups of rhesus monkeys was 4%. The seroprevalence of antibodies against human T-cell leukemia virus type 1 (HTLV-1), human immunodeficiency virus (HIV), and simian immunodeficiency virus (SIV; formerly STLV-III) was uniformly low or absent in both SAIDS-free and SAIDS-affected groups of rhesus monkeys, demonstrating that these retroviruses are not etiologically linked to SAIDS at the California Primate Research Center.
Assuntos
Síndrome da Imunodeficiência Adquirida/veterinária , Doenças dos Macacos/microbiologia , Síndrome da Imunodeficiência Adquirida/microbiologia , Síndrome da Imunodeficiência Adquirida/transmissão , Animais , Anticorpos Antivirais/análise , Ensaio de Imunoadsorção Enzimática , Feminino , Anticorpos Anti-HIV , Macaca mulatta , Troca Materno-Fetal , Doenças dos Macacos/transmissão , Gravidez , RetroviridaeRESUMO
The Mason-Pfizer monkey virus (MPMV) was reisolated from a cryopreserved sample of the original MPMV-containing rhesus breast carcinoma, and complete integrated MPMV provirus was detected in chromosomal DNA of this tumor. Reanalysis of the in vivo pathogenicity and molecular character of MPMV reisolated from the rhesus breast tumor and analysis of the original MPMV after long-term in vitro propagation in human and rhesus cells show that the original MPMV produces an acquired immunodeficiency similar to that caused by the recently described simian acquired immune deficiency syndrome type D retroviruses, and the MPMV genome and its immunosuppressive effect in vivo have remained stable despite prolonged in vitro passage in human and rhesus cells.
Assuntos
Síndrome da Imunodeficiência Adquirida/etiologia , Infecções por Retroviridae , Animais , Sequência de Bases , Enzimas de Restrição do DNA , DNA Viral/análise , Feminino , Humanos , Macaca mulatta , Neoplasias Mamárias Experimentais/microbiologia , Retroviridae/crescimento & desenvolvimento , Retroviridae/isolamento & purificaçãoRESUMO
Simian acquired immune deficiency syndrome (SAIDS) type D retrovirus (SRV) was isolated from saliva, urine, and peripheral blood mononuclear cells of a 6-year-old healthy rhesus monkey (Macaca mulatta) seronegative for antibodies to human T-lymphotropic virus (HTLV) type I, HTLV type III, and simian T-lymphotropic virus type III (STLV-III), identified as an inapparent SAIDS carrier in retrospective epidemiologic studies. This animal was linked to 34 cases of SAIDS over a 3-year period. Two juvenile rhesus monkeys inoculated iv with the SRV-containing saliva from this carrier became persistently infected with the retrovirus and developed SAIDS after 4-6 weeks. Both animals seroconverted to SRV, but neither had detectable preinoculation or postinoculation antibodies against HTLV type I, HTLV type III, or STLV-III. One of these animals died of SAIDS with disseminated cytomegalovirus infection after 24 weeks, and the other remains alive with persistent SRV viremia, generalized lymphadenopathy, and splenomegaly after a transient immunosuppression. Major clinical and pathological features associated with the newly described STLV-III were not observed. SRV was subsequently identified in saliva of 2 additional healthy carriers as well as monkeys with SAIDS. The findings of a carrier state in SAIDS and evidence for saliva transmission of the probable causative virus further support the usefulness of this animal model of nononcogenic immunosuppressive retroviral disease.
Assuntos
Síndrome da Imunodeficiência Adquirida/veterinária , Portador Sadio/veterinária , Doenças dos Macacos/transmissão , Retroviridae/isolamento & purificação , Saliva/microbiologia , Síndrome da Imunodeficiência Adquirida/transmissão , Animais , Anticorpos Antivirais/análise , Portador Sadio/microbiologia , Modelos Animais de Doenças , Feminino , Anticorpos Anti-HIV , Ativação Linfocitária , Macaca mulatta , Masculino , Mitógenos de Phytolacca americana/farmacologiaRESUMO
Simian immunodeficiency virus (SIV) variant SIVsmmPBj14 is unique in producing an acutely lethal enteropathic syndrome in pigtail macaques. To determine whether the nature of the PBj14 disease would be attenuated by decreasing virus input and to relate tissue virus burden to the severity of disease, we infected pigtail macaques with serial 10-fold doses of SIVsmmPBj14 clone bcl.3 spanning 10(-2) through 10(4)TCID50. The results revealed a strikingly narrow difference between minimum infectious and fatal disease-inducing doses and a close association between enteric lymphoid tissue virus burden and disease. All animals infected with as much as 10(4) TCID50 through as little as 100 TCID50 of virus died of the lethal PBj14 syndrome between 7 and 13 days postinfection. Animals receiving 10(-1) TCID50 became infected (PCR+) but did not develop clinical disease. Animals receiving 10(-2) TCID50 did not become infected. The clinical syndrome was surprisingly similar in all affected macaques, although the time to disease onset and total survival time increased slightly as virus input decreased from 10(4) to 10 degrees TCID50. Highest terminal virus loads in plasma, gut-associated lymphoid tissue (GALT), and lymph nodes and greatest lesion severity were attained at intermediate levels of virus input (10(1) to 10(2) TCID50), probably owing to optimal time for virus amplification in target tissues. The present study reinforces others on the PBj14 system, suggesting that once a threshold level of virus replication is attained in intestinal lymphoid tissues, the cascade of events precipitating the lethal PBj14 syndrome is triggered irreversibly.
Assuntos
Macaca nemestrina/virologia , Síndrome de Imunodeficiência Adquirida dos Símios/virologia , Vírus da Imunodeficiência Símia/patogenicidade , Animais , Anticorpos Antivirais/sangue , Especificidade de Anticorpos , Ensaio de Imunoadsorção Enzimática , Feminino , Imuno-Histoquímica , Linfonodos/virologia , Especificidade de Órgãos , Reação em Cadeia da Polimerase , Provírus/isolamento & purificação , Proteínas dos Retroviridae/sangue , Síndrome de Imunodeficiência Adquirida dos Símios/diagnóstico , Síndrome de Imunodeficiência Adquirida dos Símios/imunologia , Vírus da Imunodeficiência Símia/isolamento & purificação , Carga Viral , Proteínas Virais/isolamento & purificaçãoRESUMO
To gain insight into the unique pathogenicity of simian immunodeficiency virus (SIV) variant PBj14, which produces an acutely lethal enteropathic syndrome in infected pigtail macaques, we investigated the cell and tissue tropisms of a highly pathogenic biologic clone (bcl.3) of SIVsmmPBj14. To compare the relative amount of viral antigen in lymphoid organs of infected macaques we used an objective semiquantitative immunohistochemistry (sQIHC) assay. We found that in all animals viral antigen load was greater in alimentary-associated lymphoid tissues (gut-associated lymphoid tissue [GALT], tonsil, mesenteric and retropharyngeal lymph nodes) than in non-alimentary-associated lymphoid tissues (spleen, thymus, inguinal and axillary lymph nodes). Moreover, in six of nine animals examined, virus load in GALT was greater than that in any other lymphoid tissue. To determine whether the acute pathogenicity and prolific replication of SIVsmmPBj14 might be explained by a broader in vivo cell tropism than is typical of SIVs, we used cell subset separation and nested PCR. We found that the primary target cells in mesenteric lymph node for SIVsmmPBj14 were CD4+ T lymphocytes. However, the virus also infected macrophages, as well as CD8+ T cells and B cells, albeit at low frequencies. These results suggest that alimentary lymphoid tissue localization rather than unusual cell phenotype tropism distinguishes the singular pathogenesis of SIVsmmPBj14.
Assuntos
Síndrome de Imunodeficiência Adquirida dos Símios/virologia , Vírus da Imunodeficiência Símia/patogenicidade , Animais , Axila , Linfócitos B/virologia , Feminino , Citometria de Fluxo , Virilha , Imuno-Histoquímica , Hibridização In Situ , Intestinos , Linfonodos/virologia , Macaca nemestrina , Macrófagos/virologia , Masculino , Reação em Cadeia da Polimerase , Provírus/isolamento & purificação , RNA Viral/análise , Baço/virologia , Subpopulações de Linfócitos T/virologia , Timo/virologia , Fatores de Tempo , Tropismo , Carga Viral , Replicação ViralRESUMO
We have studied the early pathogenesis of infection by molecular clone 1.9 of SIVsmmPBj14 in pig-tailed and cynomolgus macaques. Like the uncloned PBj14 parent, SIVsmmPBj14-1.9 consistently induced an acute clinical syndrome characterized by behavioral depression, fever, profuse diarrhea, dehydration, lymphadenopathy, splenomegaly, and mucocutaneous exanthema that began at 7 days postinfection (DPI). The acute clinical disease coincided with a marked cell-associated and cell-free viremia, during which SIV p27 was demonstrated in 4 to 68% of circulating mononuclear leukocytes between 4 and 17 DPI. Also characteristic were monocytosis and reductions in CD4+ and CD8+ T lymphocytes, as well as CD20+ B lymphocytes. The most profound depletion occurred in the CD44hi subset of CD4+ T cells. Unlike animals infected previously with uncloned or biologically cloned PBj14, however, all SIVsmmPBj14-1.9-infected macaques survived the acute-phase disease to progress to a chronic, largely asymptomatic phase of infection. Recovery from the acute-phase disease correlated with down modulation of virus replication and the appearance of antibodies to SIV Env and Gag proteins. Similar to the PBj14 parent, PBj14-1.9 targeted to intestine, spleen, bone marrow, lymph node, and cerebellum. Saliva contained substantial quantities of infectious virus and no viral antibodies during the early phase of infection. By contrast, saliva from chronically infected animals usually contained antibodies but no virus. This study extends previous work demonstrating that the acute clinical syndrome produced by SIVsmmPBj14 in pig-tailed macaques represents a unique model of lentiviral pathogenesis.
Assuntos
Síndrome de Imunodeficiência Adquirida dos Símios/microbiologia , Vírus da Imunodeficiência Símia/fisiologia , Animais , Anticorpos Antivirais/biossíntese , Anticorpos Antivirais/imunologia , Sequência de Bases , Sistema Livre de Células , Sistema Nervoso Central/microbiologia , Clonagem Molecular , DNA Viral , Sistema Digestório/microbiologia , Subpopulações de Linfócitos/imunologia , Tecido Linfoide/microbiologia , Macaca fascicularis , Macaca nemestrina , Dados de Sequência Molecular , Especificidade de Órgãos/imunologia , Reação em Cadeia da Polimerase , Saliva/microbiologia , Síndrome de Imunodeficiência Adquirida dos Símios/imunologia , Síndrome de Imunodeficiência Adquirida dos Símios/fisiopatologia , Vírus da Imunodeficiência Símia/classificação , Vírus da Imunodeficiência Símia/imunologia , Vírus da Imunodeficiência Símia/isolamento & purificação , ViremiaRESUMO
We recently reported a Simian Acquired Immunodeficiency Syndrome (SAIDS) in rhesus macaques at the California Primate Research Center. Here, we studied in vitro lymphocyte response to the mitogens Concanavalin A (Con A), phytohemagglutinin (PHA) and pokeweed mitogen (PWM) with and without interleukin 2 (IL-2). Immunoglobulin (IgG and IgM) and complement (C3 and C4) concentrations were determined by radial immunodiffusion. T helper and T suppressor lymphocytes were identified with the monoclonal antibodies OKT4 and OKT8. Concentrations of IgG and IgM were significantly (p less than .05) decreased. Complement component C3 did not change but C4 was increased. The absolute lymphocyte count decreased but the OKT4:OKT8 ratio was unchanged from controls. A decreased lymphocyte response to all mitogens occurred early and became more severely depressed near death. IL-2 caused a complete or partial restoration of the response to the mitogens CON A and PHA. Both the humoral and cell mediated immune responses are affected in SAIDS. The role of IL-2 in this immune defect must be studied further.
Assuntos
Síndrome da Imunodeficiência Adquirida/veterinária , Doenças dos Macacos/imunologia , Síndrome da Imunodeficiência Adquirida/imunologia , Animais , Anticorpos Monoclonais , Proteínas do Sistema Complemento/análise , Feminino , Imunoglobulinas/análise , Técnicas In Vitro , Interleucina-2/imunologia , Ativação Linfocitária , Macaca mulatta , Masculino , Mitógenos/farmacologia , Linfócitos T/imunologia , Fatores de TempoRESUMO
Type D retrovirus was isolated from rhesus macaques with simian acquired immunodeficiency syndrome (SAIDS) and transmitted to healthy rhesus macaques with tissue culture medium containing the virus. The clinical, immunologic, and lymph node morphologic changes were observed in 9 rhesus macaques for 52 weeks after inoculation. A spectrum of clinical signs developed including early death, persistent SAIDS, and apparent remission. Animals that died or developed persistent SAIDS had characteristic lymphoid depletion, persistently depressed peripheral blood mononuclear cell (PBMC) mitogenic response, and decreased serum immunoglobulins. The SAIDS retrovirus (SRV) was recovered from PBMC of 8 of the animals after inoculation. Virus could not be recovered from PBMC of one animal in remission, but this animal developed serum-neutralizing antibodies to SRV after inoculation. Seven of the animals seroconverted to SRV after inoculation, all 9 were seronegative for human T-lymphotropic virus-III, and 5 animals tested were seronegative to human T-lymphotropic virus-I. These findings support the etiologic role of the type D retrovirus in SAIDS and further define the pathogenesis of this disease.
Assuntos
Síndrome da Imunodeficiência Adquirida/microbiologia , Macaca mulatta/microbiologia , Macaca/microbiologia , Retroviridae/patogenicidade , Síndrome da Imunodeficiência Adquirida/imunologia , Animais , Feminino , Imunoglobulinas/análise , Masculino , Mitógenos , Retroviridae/isolamento & purificaçãoRESUMO
Since August 25, 1981, an outbreak of simian acquired immunodeficiency syndrome ( SAIDS ) has been recognized in a single outdoor corral housing 77 rhesus monkeys (Macaca mulatta) over a 16-month period. The etiology of this syndrome is unknown but epidemiologic evidence suggests an infectious agent. Thirty-two cases of SAIDS have been identified (31 female, 1 male), and 27 of these animals have died (case fatality rate = 84%). Three of these deaths occurred among 13 infants born in the corral . All 27 deaths were females. For animals in the original cohort, sex was not a statistically significant risk factor. For animals born in the corral females were at greater risk (p = 0.0489; Fisher's Exact Test). SAIDS mortality rates were highest for animals entering the corral at less than 30 months of age (4.4 deaths per 100 monkey months of follow-up) and for animals born into the cage (3.3 deaths per 100 monkey-months of follow-up). The mortality rate was lowest for animals entering the corral at greater than 30 months of age, (0.32 deaths per 100 monkey-months of follow-up). No significant associations were found for the factors weaning history, cage-move history, parentage, generation, and medical history, including history of bite-wound trauma. Nine of the original 64 animals entering the corral on August 25, 1981, were previously associated with a group of 110 rhesus monkeys occupying this same corral from September 1976 to August 1981. Though less dramatic, a similar pattern of morbidity and high mortality was recognized retrospectively in this group.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Síndrome da Imunodeficiência Adquirida/veterinária , Animais de Laboratório , Surtos de Doenças/veterinária , Macaca mulatta , Macaca , Doenças dos Macacos/mortalidade , Síndrome da Imunodeficiência Adquirida/mortalidade , Fatores Etários , Animais , California , Feminino , Fibrossarcoma/epidemiologia , Fibrossarcoma/veterinária , Masculino , Doenças dos Macacos/epidemiologia , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/veterináriaRESUMO
The thyroxine (T4) and triiodothyronine (T3) response of the female baboon to injection of exogenous thyroid stimulating hormone was studied. This response established reference values for baseline and post-stimulation serum levels of T4 and T3. The reference values for T4 and T3 by radioimmunoassay were 9.9 +/- 2.2 micrograms/dl and 121 +/- 18 ng/dl, respectively. The T4 response to thyroid-stimulating hormone reached its peak level of 22.7 +/- 1.8 micrograms/dl at 12 +/- 2.5 hours. The corresponding peak response for the T3 was 351 +/- 61 ng/dl which occurred at 8.0 +/- 2.5 hours. The T3 response was more rapid and reached its peak earlier than T4.
Assuntos
Papio/sangue , Tireotropina/farmacologia , Tiroxina/sangue , Tri-Iodotironina/sangue , Animais , Feminino , Radioimunoensaio/veterinária , Valores de Referência , Tireotropina/fisiologiaRESUMO
A syndrome of acquired immunodeficiency within a group of outdoor-housed rhesus macaques (Macaca mulatta) with unusually high mortality has been identified at the California Primate Research Center. The cause of death for most of the affected animals included septicemia and/or chronic diarrhea with wasting, often complicated by other problems. In many cases, multiple or unusual infectious agents were isolated or recognized, including cytomegalovirus, Cryptosporidium spp., and Candida albicans. Septicemias due to usually innocuous agents such as Staphylococcus epidermidis and Alcaligenes faecalis were seen. Two animals developed cutaneous fibrosarcomas. Affected animals had generalized lymphadenopathy and splenomegaly, with depletion of T-cell populations, initially follicular hyperplasia followed by depletion, and absence of plasma cells. This spontaneous disease syndrome in nonhuman primates has similarities to acquired immune deficiency syndrome (AIDS) in humans, providing an animal model for the study of the complex factors modulating the immune system.
Assuntos
Síndrome da Imunodeficiência Adquirida/patologia , Macaca mulatta/imunologia , Macaca/imunologia , Síndrome da Imunodeficiência Adquirida/epidemiologia , Síndrome da Imunodeficiência Adquirida/veterinária , Animais , California , Sistema Digestório/patologia , Modelos Animais de Doenças , Feminino , Fibrossarcoma/patologia , Fibrossarcoma/ultraestrutura , Hepatomegalia/patologia , Humanos , Pulmão/patologia , Linfonodos/patologia , Masculino , Pele/lesões , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/ultraestrutura , Baço/patologiaRESUMO
Simian acquired immunodeficiency syndrome is a fatal immunosuppressive disease caused by type D retroviruses such as simian acquired immunodeficiency syndrome retrovirus type 1 (SRV-1). The disease is characterized by generalized lymphadenopathy, opportunistic infections, and lymphoid depletion with defects in both humoral and cell-mediated immunity. To understand how SRV-1 infection relates to the immune defect, we studied in vivo-infected lymphocytes from SRV-1-positive macaques with and without clinical signs of immunosuppressive disease. B and T helper/inducer and T suppressor/cytotoxic lymphocytes were purified by panning or by flow cytometry. Neutrophils were purified by dextran sedimentation, and platelets were purified by low-speed centrifugation. In vitro infection studies were also done with HUT78, H9, K562, rhesus lung fibroblast, rhesus monkey kidney, and bat lung cells. SRV-1 in lymphocytes or culture supernatants was detected by the induction of syncytia in cocultivated Raji cells and was confirmed by immunofluorescence, electron microscopy, or reverse transcriptase assay. We found that B and T helper/inducer lymphocytes were infected in all animals tested. The number of infected T suppressor/cytotoxic cells was generally lower than that of the other cell subsets, and not all animals in this subset had SRV-1 infections. All other cells exposed in vitro to SRV-1, except bat lung cells, were able to be infected. These findings show that SRV-1 has a broad cell tropism for lymphoid and nonlymphoid cell types.
Assuntos
Síndrome da Imunodeficiência Adquirida/veterinária , Doenças dos Macacos/imunologia , Retroviridae/patogenicidade , Síndrome da Imunodeficiência Adquirida/imunologia , Animais , Formação de Anticorpos , Linhagem Celular , Feminino , Citometria de Fluxo , Imunidade Celular , Macaca mulatta , Masculino , Doenças dos Macacos/microbiologia , Linfócitos T Auxiliares-Indutores/microbiologia , Linfócitos T Reguladores/microbiologiaRESUMO
A syndrome closely resembling acquired immunodeficiency syndrome (AIDS) in man has been identified in a group of 64 rhesus monkeys (Macaca mulatta) maintained outdoors at the California Primate Research Center. The syndrome is characterised by generalised lymphadenopathy, severe opportunistic infections including cytomegalovirus, chronic wasting, and high mortality. In 1 animal a multifocal cutaneous fibrosarcoma developed. This syndrome in monkeys may provide an animal model for human AIDS.
Assuntos
Síndrome da Imunodeficiência Adquirida/veterinária , Modelos Animais de Doenças , Surtos de Doenças/veterinária , Macaca mulatta/imunologia , Macaca/imunologia , Doenças dos Macacos/imunologia , Síndrome da Imunodeficiência Adquirida/mortalidade , Síndrome da Imunodeficiência Adquirida/patologia , Animais , Infecções Bacterianas/imunologia , Infecções Bacterianas/mortalidade , Infecções Bacterianas/veterinária , California , Feminino , Fibrossarcoma/imunologia , Fibrossarcoma/veterinária , Masculino , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/veterinária , Síndrome , Viroses/imunologia , Viroses/mortalidade , Viroses/veterináriaRESUMO
We compared the efficacy of immunization with either simian immunodeficiency virus (SIV) Env glycoprotein (Env), Env plus Gag proteins (Gag-Env), or whole inactivated virus (WIV), with or without recombinant live vaccinia vector (VV) priming, in protecting 23 rhesus macaques (six vaccine and two control groups) from challenge with SIVmac251 clone BK28. Vaccination elicited high titers of syncytium-inhibiting and anti-Env (gp120/gp160) antibodies in all vaccinated macaques and anti-Gag (p27) antibodies in groups immunized with WIV or Gag-Env. Only WIV-immunized macaques developed anticell (HuT78) antibodies. After homologous low-dose intravenous virus challenge, we used frequency of virus isolation, provirus burden, and change in antibody titers to define four levels of resistance to SIV infection as follows. (i) No infection ("sterilizing" immunity) was induced only in WIV-immunized animals. (ii) Abortive infection (strong immunity) was defined when virus or provirus were detected early in the postchallenge period but not thereafter and no evidence of virus or provirus was detected in terminal tissues. This response was observed in two animals (one VV-Env and one Gag-Env). (iii) Suppression of infection (incomplete or partial immunity) described a gradient of virus suppression manifested by termination of viremia, declining postchallenge antibody titers, and low levels (composite mean = 9.1 copies per 10(6) cells) of provirus detectable in peripheral blood mononuclear cells or lymphoid tissues at termination (40 weeks postchallenge). This response occurred in the majority (8 of 12) of subunit-vaccinated animals. (iv) Active infection (no immunity) was characterized by persistent virus isolation from blood mononuclear cells, increasing viral antibody titers postchallenge, and high levels (composite mean = 198 copies per 10(6) cells) of provirus in terminal tissues and blood. Active infection developed in all controls and two of three VV-Gag-Env-immunized animals. The results of this study restate the protective effect of inactivated whole virus vaccines produced in heterologous cells but more importantly demonstrate that a gradient of suppression of challenge virus growth, reflecting partial resistance to SIV infection, is induced by subunit vaccination. The latter finding may be pertinent to studies with human immunodeficiency virus vaccines, in which it is plausible that vaccination may elicit significant suppression of virus infection and pathogenicity rather than sterilizing immunity.
Assuntos
Imunoterapia Ativa , Glicoproteínas de Membrana , Síndrome de Imunodeficiência Adquirida dos Símios/prevenção & controle , Vacinação , Vacinas Sintéticas , Proteínas do Envelope Viral , Vacinas Virais , Animais , Anticorpos Antivirais/sangue , Sequência de Bases , Sangue/microbiologia , Células Cultivadas , Produtos do Gene gag/genética , Produtos do Gene gag/imunologia , Proteína gp120 do Envelope de HIV/genética , Proteína gp120 do Envelope de HIV/imunologia , Humanos , Imunização Secundária , Ativação Linfocitária , Macaca mulatta , Dados de Sequência Molecular , Testes de Neutralização , Provírus/isolamento & purificação , Proteínas Recombinantes/imunologia , Síndrome de Imunodeficiência Adquirida dos Símios/imunologia , Síndrome de Imunodeficiência Adquirida dos Símios/patologia , Vírus da Imunodeficiência Símia/crescimento & desenvolvimento , Vaccinia virus/genéticaRESUMO
Infection of pigtail macaques with SIVsmmPBj14, biological clone 3 (SIV-PBj14-bc13), produces an acute and usually fatal shock-like syndrome 7 to 14 days after infection. We used this simian immunodeficiency virus (SIV) model as a rapid and rigorous challenge to evaluate the efficacy of two SIV Env vaccine strategies. Groups of four pigtail macaques were immunized four times over a 25-week span with either a recombinant Semliki Forest virus expressing the SIV-PBj14 Env gp160 (SFV-SIVgp160) or purified recombinant SIV-PBj14 gp120 (rgp120) in SBN-1 adjuvant. Antibody titers to SIV Env developed in all immunized animals (mean peak titers prior to challenge, 1:1,700 for SFV-SIV gp 160 and 1:10,500 for rgp120), but neither neutralizing antibodies nor SIV-specific T-cell proliferative responses were detectable in any of the vaccinees. All macaques were challenged with a 100% infectious, 75% fatal dose of SIV-PBj14-bc13 at week 26. Three of four control animals died of acute SIV-PBj14 syndrome on days 12 and 13. By contrast, all four SFV-SIVgp160-immunized animals and three of the four rgp120-immunized animals were protected from lethal disease. While all virus-challenged animals became infected, symptoms of the SIV-PBj14 syndrome were more severe in controls than in vaccinees. Mean virus titers in plasma at 13 days postchallenge were approximately 10-fold lower in vaccinated than control animals. However, there was no apparent correlation between survival and levels of peripheral blood mononuclear cell-associated culturable virus, provirus load, or any antiviral immunologic parameter examined. The results indicate that while immunization with SFV-SIVgp160 and rgp120 did not protect against virus infection, these Env vaccines did lower the virus load in plasma and protect against the lethal SIV-PBj14 challenge.
Assuntos
Produtos do Gene env/imunologia , Proteína gp120 do Envelope de HIV/imunologia , Glicoproteínas de Membrana , Vacinas contra a SAIDS/imunologia , Vírus da Floresta de Semliki/imunologia , Síndrome de Imunodeficiência Adquirida dos Símios/prevenção & controle , Vírus da Imunodeficiência Símia/imunologia , Proteínas do Envelope Viral , Animais , Anticorpos Antivirais/imunologia , Sequência de Bases , Contagem de Linfócito CD4 , Linhagem Celular , Células Cultivadas , Cricetinae , DNA Viral , Feminino , Produtos do Gene env/genética , Vetores Genéticos/genética , Proteína gp120 do Envelope de HIV/genética , Humanos , Imunidade Celular , Macaca nemestrina , Camundongos , Dados de Sequência Molecular , Vírus da Floresta de Semliki/genética , Síndrome de Imunodeficiência Adquirida dos Símios/mortalidade , Vírus da Imunodeficiência Símia/química , Vírus da Imunodeficiência Símia/crescimento & desenvolvimento , Vacinas Sintéticas/imunologiaRESUMO
A new serotype of simian acquired immune deficiency syndrome (SAIDS) retrovirus (type 2) belonging to the D genus of retroviruses is associated with a SAIDS occurring spontaneously in a colony of Celebes macaques (Macaca nigra) and rhesus macaques (Macaca mulatta) at the Oregon Regional Primate Research Center. This syndrome resembles SAIDS in M. mulatta at the California Primate Research Center, which is associated with a similar type D retrovirus (type 1). However, at the Oregon Center, SAIDS is distinguished by the occurrence of retroperitoneal fibromatosis in some of the affected monkeys. Type 2 virus was isolated from seven of seven macaques with SAIDS, retroperitoneal fibromatosis, or both and from one of six healthy macaques. The new strain is closely related to SAIDS retrovirus type 1 and Mason-Pfizer monkey virus but can be distinguished by competitive radioimmunoassay for minor core (p10) antigen and by genomic restriction endonuclease cleavage patterns. Neutralization tests indicate that type 1 and type 2 SAIDS retroviruses are distinct serotypes. Therefore, separate vaccines may be necessary to control these infections in colonies of captive macaques.
Assuntos
Síndrome da Imunodeficiência Adquirida/veterinária , Macaca/microbiologia , Doenças dos Macacos/microbiologia , Retroviridae/isolamento & purificação , Síndrome da Imunodeficiência Adquirida/microbiologia , Animais , Enzimas de Restrição do DNA , Microscopia Eletrônica , RNA Viral/análise , Retroviridae/classificação , Retroviridae/ultraestrutura , Proteínas dos Retroviridae/análise , SorotipagemRESUMO
A syndrome of acquired immunodeficiency has been identified in a group of rhesus monkeys (Macaca mulatta) which died at the California Primate Research Center. Clinical evaluation of these animals revealed that 50% or more had lymphadenopathy, weight loss, and diarrhea. At least 30% had splenomegaly, fever, cutaneous abscesses and/or arthritis/myositis. Two animals had fibrosarcomas. Anemia was seen in 19 animals, lymphopenia in 14, granulocytopenia in four and thrombocytopenia in three. Hepatitis was diagnosed histopathologically in 13. Electrophoresis revealed hypoproteinemia, hypoalbuminemia and hypogammaglobulinemia. Numerous bacterial, protozoal, and viral agents were identified including cytomegalovirus and leukocyte-associated herpesvirus. Pathologic lesions included severe post-reactive depletion of lymphocytes in germinal centers and paracortical regions of lymph nodes. Clinical and pathologic changes indicate an acquired immunodeficiency syndrome which has some similarities to AIDS in humans. This disease in monkeys may provide a model for studying that disease.
Assuntos
Síndrome da Imunodeficiência Adquirida/veterinária , Animais de Laboratório , Surtos de Doenças/veterinária , Macaca mulatta , Macaca , Doenças dos Macacos/fisiopatologia , Síndrome da Imunodeficiência Adquirida/fisiopatologia , Animais , Anticorpos Antivirais/análise , Contagem de Células Sanguíneas/veterinária , Análise Química do Sangue , California , Citomegalovirus/imunologia , Feminino , Linfonodos/patologia , MasculinoRESUMO
A disease that is similar to human AIDS may occur in monkeys. Simian AIDS (SAIDS) was experimentally transmitted from 2 rhesus monkeys dying of the disease to 4 cytomegalovirus (CMV) antibody-negative rhesus monkeys. The inocula consisted of the supernatant fluid from 10% homogenates of various tissues with or without buffy-coat cells from blood. Lymphadenopathy, splenomegaly, neutropenia, polymyositis, and other signs of the disease appeared in recipients within a few weeks after inoculation. Two animals developed Kaposi-like "patch" and "plaque" skin lesions and one died of sepsis and profound lymphoid depletion. A second animal also died with lymphoid depletion. All animals became infected with CMV but antibody levels were low in two animals, appeared and then disappeared in one, and never developed in the second monkey which died.