RESUMEN
Pathogenic simian immunodeficiency virus (SIV) infection is associated with enteropathy, which likely contributes to AIDS progression. To identify candidate etiologies for AIDS enteropathy, we used next-generation sequencing to define the enteric virome during SIV infection in nonhuman primates. Pathogenic, but not nonpathogenic, SIV infection was associated with significant expansion of the enteric virome. We identified at least 32 previously undescribed enteric viruses during pathogenic SIV infection and confirmed their presence by using viral culture and PCR testing. We detected unsuspected mucosal adenovirus infection associated with enteritis as well as parvovirus viremia in animals with advanced AIDS, indicating the pathogenic potential of SIV-associated expansion of the enteric virome. No association between pathogenic SIV infection and the family-level taxonomy of enteric bacteria was detected. Thus, enteric viral infections may contribute to AIDS enteropathy and disease progression. These findings underline the importance of metagenomic analysis of the virome for understanding AIDS pathogenesis.
Asunto(s)
Caliciviridae/aislamiento & purificación , Intestinos/virología , Parvoviridae/aislamiento & purificación , Picornaviridae/aislamiento & purificación , Síndrome de Inmunodeficiencia Adquirida del Simio/virología , Virus de la Inmunodeficiencia de los Simios/fisiología , Animales , Caliciviridae/clasificación , Caliciviridae/genética , Chlorocebus aethiops , Heces/microbiología , Heces/virología , Intestinos/microbiología , Datos de Secuencia Molecular , Parvoviridae/clasificación , Parvoviridae/genética , Filogenia , Picornaviridae/clasificación , Picornaviridae/genética , Reacción en Cadena de la Polimerasa , Síndrome de Inmunodeficiencia Adquirida del Simio/microbiología , Virus de la Inmunodeficiencia de los Simios/patogenicidadRESUMEN
The rhesus macaque (Macaca mulatta) is used extensively in translational biomedical research and drug development studies and is an important model of aging. Macaques often develop myocardial fibrosis with age, which can result in the loss of normal cardiac architecture with the expansion of the extracellular matrix and deposition of collagen. The etiology and pathogenesis of this pernicious process is poorly understood. Cardiac fibrosis was assessed using histologic and immunohistochemical techniques in cardiac tissue sections from 34 rhesus macaques. Overall left ventricular and left ventricular mid-myocardial interstitial/perivascular fibrosis were positively correlated with age (r = .6522, p < .0001 and r = .4704, p = .005, respectively). When divided into young (mean = 2.8 years), middle-aged (mean = 17.5 years), and advanced age (mean = 29.2 years) groups, immunophenotypic characterization of antigen presenting cells revealed differential expression of CD163 and DC-SIGN between the young and middle-aged groups compared to the advanced age group (p < .0001). HAM-56 expression decreased significantly in the advanced age cohort (p = .0021). The expression of CD8, CD163, and DC-SIGN correlated positively with age (r = .3999, p = .0191; r = .5676, p = .0005; r = .5245, p = .0014, respectively). These results show the importance of myocardial fibrosis as a common age-related pathology and additionally, alterations in T cell, macrophage, and dendritic cell phenotype in rhesus macaque myocardium are associated with age but unassociated with the fibrosis.