RESUMEN
SAIDS-associated lymphoma (SAL) represents a monoclonal expansion of B-cell origin in which simian immunodeficiency virus (SIV) infection is not detected. However, tumor cells are frequently infected with rhesus lymphocryptovirus (RhLCV), a rhesus homologue of Epstein-Barr virus (EBV). In previous studies, the incidence of RhLCV infection in SAL was determined to be 89% as measured by polymerase chain reaction (PCR) and/or in situ hybridization. The main objective of the present study was to ascertain whether the level of RhLCV infection in the SIV-infected macaque is influenced as a function of SAIDS progression, and/or whether increased levels of RhLCV infection may correlate with the development of SAL. To this end, RhLCV infection was evaluated in three independent groups: (1) in lymphomas from SIV-infected rhesus macaques, (2) in peripheral blood mononuclear cells (PBMC) from a cohort of 69 randomly selected healthy animals, and (3) in PBMC collected from 22 SIV-infected animals at various times during progression to SAIDS or SAL. The relative levels of RhLCV infection were evaluated by PCR/Southern blot analysis, visual comparison to a standard dilution series, and assignment of relative signal intensity to a uniform classification scheme. The data show that SIV-infected monkeys have a generally higher RhLCV load in PBMC than do healthy animals, but that the virus load varies widely among animals during disease progression. Increased RhLCV load does not occur uniformly during the progression of SAIDS, although evidence indicates an increased RhLCV viral load in the development of SAL.
Asunto(s)
Infecciones por Herpesviridae/complicaciones , Lymphocryptovirus , Linfoma de Células B/virología , Síndrome de Inmunodeficiencia Adquirida del Simio/complicaciones , Infecciones Tumorales por Virus/complicaciones , Animales , Southern Blotting , Progresión de la Enfermedad , Infecciones por Herpesviridae/virología , Macaca mulatta , Reacción en Cadena de la Polimerasa , Distribución Aleatoria , Síndrome de Inmunodeficiencia Adquirida del Simio/virología , Infecciones Tumorales por Virus/virología , Carga ViralRESUMEN
Non-Hodgkin's lymphomas occur with increased frequency (3-6%) in HIV-infected individuals. These AIDS-associated lymphomas (AALs) exhibit characteristics that distinguish them from lymphomas in the general population. A proposed model for the pathogenesis of AAL includes the following: (1) Tumorigenesis is multistep; (2) tumors occur in long-term survivors; (3) tumors are of clonal B cell origin; (4) HIV acts early and is an indirect effector; (5) tumor cells are infected with EBV; and (6) specific genetic lesions occur in tumor cells. Many aspects of this process remain to be tested in an animal model system. Since 1984, necropsy examinations have been performed on more than 1000 SIV-infected rhesus and cynomolgus monkeys at the Tulane Regional Primate Research Center. Lymphoid malignancies were detected in a proportion of SIV-infected animals. These SAIDS-associated lymphomas (SALs) have been studied to determine the extent to which their pathological features recapitulate a working model for the pathogenesis of AAL. The results show that lymphomas occur in SIV-infected rhesus macaques at 4% incidence, similar to that of AAL, and that the incidence of SAL in cynomolgus macaques is eightfold higher. Analysis of SAL from both species of macaques demonstrated significant similarity to the hallmark pathobiological features of AAL. These findings indicate that the HIV-infected human and the SIV-infected macaque share a common pathobiology and mechanism of lymphomagenesis.
Asunto(s)
Linfoma Relacionado con SIDA/veterinaria , Linfoma no Hodgkin/patología , Enfermedades de los Monos/patología , Síndrome de Inmunodeficiencia Adquirida del Simio/patología , Virus de la Inmunodeficiencia de los Simios , Animales , Secuencia de Bases , Southern Blotting , ADN Viral/análisis , ADN Viral/aislamiento & purificación , Humanos , Inmunohistoquímica , Hibridación in Situ , Linfoma Relacionado con SIDA/patología , Linfoma Relacionado con SIDA/virología , Linfoma no Hodgkin/virología , Macaca fascicularis , Macaca mulatta , Datos de Secuencia Molecular , Reacción en Cadena de la Polimerasa , Síndrome de Inmunodeficiencia Adquirida del Simio/virología , Virus de la Inmunodeficiencia de los Simios/genéticaRESUMEN
To determine whether functional antibody responses correlate with factors associated with severe measles, measles-specific antibody-dependent cellular cytotoxicity (ADCC) and neutralizing antibodies were measured in 114 Filipino children with measles. Children > 24 months old were more likely to have ADCC antibody in acute sera than were those < or = 24 months (odds ratio = 3.6, 95% confidence interval = 1.7-7.8). This age-related difference in ADCC prevalence was most apparent between younger and older girls. Among children < or = 24 months, a higher prevalence of ADCC antibody was associated with male sex, absence of lymphopenia, and household exposure to measles. The presence of ADCC antibody was not associated with malnutrition or diarrhea. Neutralizing antibody titers were lower in children with lymphopenia but showed no relationship with the other variables. Thus, the ADCC antibody response is associated with some risk factors related to measles severity. Attenuation of this response may contribute to the severity of infection.
Asunto(s)
Anticuerpos Antivirales/sangre , Citotoxicidad Celular Dependiente de Anticuerpos , Sarampión/inmunología , Enfermedad Aguda , Factores de Edad , Preescolar , Femenino , Humanos , Lactante , Masculino , Sarampión/transmisión , Factores SexualesRESUMEN
Antibody titers measured in functional and immunofluorescent assays were compared with proportions of peripheral blood mononuclear cells infected with measles virus in 8 adults with measles. In addition, a syncytium inhibition assay (SIA) for measuring neutralizing antibody using low-passage virus was compared with a standard plaque neutralization test (PNT). Antibody-dependent cellular cytotoxicity (ADCC) antibody rose later but attained higher titer than neutralizing, antibody-dependent complement-mediated lysis, IgM, or IgG antibodies. When titer changes between specimens from each patient obtained on different days were compared, only ADCC (r = .81, P = .026) and IgM (r = .81, P = .027) antibodies correlated with reductions in viremia. SIA and PNT correlated well (r = .93, P < .001). ADCC may be an important defense against measles. The delay in ADCC antibody relative to other antibodies is unique among viruses studied. The SIA is a useful alternative to the PNT for measuring measles neutralizing antibody.