A majority of individuals infected with human immunodeficiency virus (HIV) have inadequate access to antiretroviral therapy and ultimately develop debilitating oral infections that often correlate with disease progression. Due to the impracticalities of conducting host-microbe systems-based studies in HIV infected patients, we have evaluated the potential of simian immunodeficiency virus (SIV) infected rhesus macaques to serve as a non-human primate model for oral manifestations of HIV disease. We present the first description of the rhesus macaque oral microbiota and show that a mixture of human commensal bacteria and “macaque versions” of human commensals colonize the tongue dorsum and dental plaque. Our findings indicate that SIV infection results in chronic activation of antiviral and inflammatory responses in the tongue mucosa that may collectively lead to repression of epithelial development and impact the microbiome. In addition, we show that dysbiosis of the lingual microbiome in SIV infection is characterized by outgrowth of Gemella morbillorum that may result from impaired macrophage function. Finally, we provide evidence that the increased capacity of opportunistic pathogens (e.g. E. coli) to colonize the microbiome is associated with reduced production of antimicrobial peptides.

/pdf/transcription-profiling-reveals-potential-mechanisms-of-5c2i96krvl.pdf

Transcription profiling reveals potential mechanisms of dysbiosis in the oral microbiome of rhesus macaques with chronic untreated SIV infection.

Background The development of susceptibility to secondary pathogenic infections in the oral cavity during HIV infection is likely to result from or coincide with deterioration of the local mucosal immune system. Methods We have utilized the SIV model to investigate the kinetics and magnitude of oral pathogenesis during systemic dissemination of intravenously inoculated SIVmac251. Results Viral replication was detected in oropharyngeal lymph nodes at 6 weeks post-infection and shown to be coincident with a broad scale loss of growth factor receptor transcription in the oral mucosa, providing multiple avenues for blocking the normal activity of apoptosis inhibitors that function through Bcl2- and p53-dependent pathways. Conclusions Our findings suggest that the normal balance between cell death and regeneration may be rapidly disrupted in the oral mucosa during the early stages of immunodeficiency virus infection, setting the stage for continuing deterioration of immune function and the development of susceptibility to secondary infections.

George

Papers

Loss of growth factor receptor signaling in the oral mucosa during primary SIV infection may enhance apoptosis and promote pathogenesis