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Interactions between HIV, microorganisms and immune humoral factors in HIV-2 and HIV-1 infection
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The present research project had the objective of determining the different interactions between host and bacteria in the oral cavity of untreated HIV-2 and HIV-1 infected subjects. More specifically, oral health patterns, salivary Th1/Th2 cytokine response, and oral bacterial diversity and quantitative presence of pathogenic species were evaluated. The first phase of this study involved the recruitment of 60 subjects divided in 3 study groups according to HIV status (HIV-1, HIV-2 and HIV negative) in a cross-sectional study. Clinical data focusing oral and systemic health and biological samples (saliva and plaque) were collected. To evaluate the role of the host in controlling HIV and other pathogens in the oral cavity, saliva samples were tested in vitro for their activity against HIV isolates and Th1 and Th2 cytokines were measured in these samples. Bacterial colonization in saliva and plaque samples was analyzed for diversity and relative quantitation of specific pathogenic species. The specific effect of bacteria in HIV replication was investigated. Finally, retrieved data was combined to investigate the presence of associations between variables. It was observed that, globally, HIV-2 and HIV-1 subjects had a similar oral health profile, which was impaired comparing to HIV-negative subjects. Overall, HIV-2 oral health condition was between HIV-1 infected and healthy subjects. The results of the inhibition study suggest that HIV-2 is less susceptible to inhibition by saliva, while saliva inhibitory activity against HIV-1 and HIV-2 is more prevalent in HIV-2 infected subjects. HIV-1 subjects have an increase in oral Th2 associated cytokines, which is not observed in HIV-2 subjects. Microbiological studies show an increase of P. gingivalis in plaque samples of HIV-2 subjects, and suggest the presence of shifts in oral microbial population specific to HIV type. It was also observed that in vitro reactivation by periodontal pathogens seems to be an independent mechanism of viral reactivation of latent HIV-1 but not HIV- 2, which needs additional TNF-alpha-induced inflammation. As a global conclusion, HIV-2, unlike HIV-1 infection, is associated to a rather conserved oral homeostasis, with host response potentially controlling viral replication and bacterial colonization. Further longitudinal studies with larger sample sizes are necessary to determine the potential causal relationship between the conserved oral homeostasis and the attenuated systemic behavior in HIV-2 infection.
Descrição
Tese de doutoramento, Medicina Dentária (Biologia Oral), Universidade de Lisboa, Faculdade de Medicina Dentária, 2015
Palavras-chave
Lesões da mucosa oral Infecção cruzada HIV-1 HIV-2 Teses de doutoramento - 2014