HIV-associated salivary gland disease: a role for BK birus

HIV-associated salivary gland disease (HIV-SGD) is disfiguring and causes significant morbidity in the HIV population. Evidence detailing the epidemiology of HIV-SGD suggests the involvement of a viral opportunist in its pathogenesis, yet the specific etiology of HIV-SGD remains unclear. To determine the role for an opportunistic virus as the etiologic agent of HIV-SGD, we hypothesized that HIV-SGD was a manifestation of primary infection or reactivation with a DNA tumor virus, BKV, during immune suppression. The central hypothesis of this work is that viral pathogenesis is essential to the development of salivary gland disease. Results show for the first time that polyomavirus, BKV, is associated with HIV-SGD. BKV DNA, RNA, and protein were consistently detected in salivary gland biopsies and in the peripheral blood and oral fluids from HIV-SGD patients and not in control subjects

BK virus has tropism for human salivary gland cells in vitro: Implications for transmission

BACKGROUND: In this study, it was determined that BKV is shed in saliva and an in vitro model system was developed whereby BKV can productively infect both submandibular (HSG) and parotid (HSY) salivary gland cell lines. RESULTS: BKV was detected in oral fluids using quantitative real-time PCR (QRTPCR). BKV infection was determined using quantitative RT-PCR, immunofluorescence and immunoblotting assays. The infectivity of BKV was inhibited by pre-incubation of the virus with gangliosides that saturated the major capsid protein, VP1, halting receptor mediated BKV entry into salivary gland cells. Examination of infected cultures by transmission electron microscopy revealed 45-50 nm BK virions clearly visible within the cells. Subsequent to infection, encapsidated BK virus was detected in the supernatant. CONCLUSION: We thus demonstrated that BKV was detected in oral fluids and that BK infection and replication occur in vitro in salivary gland cells. These data collectively suggest the potential for BKV oral route of transmission and oral pathogenesis

HIV-associated salivary gland disease: a role for BK birus

HIV-associated salivary gland disease (HIV-SGD) is disfiguring and causes significant morbidity in the HIV population. Evidence detailing the epidemiology of HIV-SGD suggests the involvement of a viral opportunist in its pathogenesis, yet the specific etiology of HIV-SGD remains unclear. To determine the role for an opportunistic virus as the etiologic agent of HIV-SGD, we hypothesized that HIV-SGD was a manifestation of primary infection or reactivation with a DNA tumor virus, BKV, during immune suppression. The central hypothesis of this work is that viral pathogenesis is essential to the development of salivary gland disease. Results show for the first time that polyomavirus, BKV, is associated with HIV-SGD. BKV DNA, RNA, and protein were consistently detected in salivary gland biopsies and in the peripheral blood and oral fluids from HIV-SGD patients and not in control subjects

Human BK Polyomavirus—The Potential for Head and Neck Malignancy and Disease

Members of the human Polyomaviridae family are ubiquitous and pathogenic among immune-compromised individuals. While only Merkel cell polyomavirus (MCPyV) has conclusively been linked to human cancer, all members of the polyomavirus (PyV) family encode the oncoprotein T antigen and may be potentially carcinogenic. Studies focusing on PyV pathogenesis in humans have become more abundant as the number of PyV family members and the list of associated diseases has expanded. BK polyomavirus (BKPyV) in particular has emerged as a new opportunistic pathogen among HIV positive individuals, carrying harmful implications. Increasing evidence links BKPyV to HIV-associated salivary gland disease (HIVSGD). HIVSGD is associated with elevated risk of lymphoma formation and its prevalence has increased among HIV/AIDS patients. Determining the relationship between BKPyV, disease and tumorigenesis among immunosuppressed individuals is necessary and will allow for expanding effective anti-viral treatment and prevention options in the future

Bacteria-mediated reactivation of gammaherpesviruses

Significant morbidity is associated with the synergistic and inhibitory interactions of bacteria, viruses, parasites, and fungi. The oral cavity, gut, and genitourinary tract are home to many of these organisms and are the site of virus-associated malignancies that affect millions worldwide. Yet little is known with regard to the cellular and molecular interactions of viral pathogens with the normal flora as well as the interactions among pathogens themselves. Our laboratory is interested in understanding the role of factors present within the immediate environment that may influence reactivation of persistent infection and pathogenesis. Our central hypothesis is that viral-bacterial interactions foster enhanced pathogen replication and modulation of the immune response in the mouth, GI tract, and genito-urinary tract. The detection of replicating virus in these tissues has incited investigation into the relationship between bacterial infection and herpesviral reactivation. We hypothesized that bacterial end-products including short chain fatty acids (SCFA), lipopolysaccharide (LPS), and lipoteichoic acid (LTA) secreted by oral bacteria initiate viral reactivation from latency. Latently infected EBV, KSHV, and MHV 68 cell lines were incubated with crude spent media containing secreted SCFA, and components of bacterial pathogens (E. faecalis, Bacteriodes, Prevotella, Porphomonas, and Fusiobacterium Nucleatum). Cells were then assayed for viral promoter activation, promoter-protein interactions, and state of infection. Following incubation with crude spent media, viral immediate early promoters were activated, the viral early genes were upregulated as determined by RT PCR and western blot, and linear genomes were detected. HDAC inhibition activity as well as protein kinase C activity increased significantly following treatment with bacterial spent media. KSHV and EBV were consistently reactivated by bacterial metabolites but the mechanism of reactivation was both bacteria, virus, and cell type specific. Interestingly, EBV was preferentially reactivated following toll like receptor stimulation while KSHV and HSV-1 reactivation occurred following HDAC inhibition. In conclusion, these studies provide significant insights to gammaherpesreactivation that may occur in vivo via pathogen-pathogen interaction

Oral Cytokine Levels Are More Linked to Levels of Plasma and Oral HIV-1 RNA Than to CD4+ T-Cell Counts in People With HIV.

BackgroundWe determined the levels of 11 soluble immune mediators in oral washings of AIDS Clinical Trials Group A5254 participants with varying degrees of plasma viremia and CD4 T-cell counts to characterize the mucosal immune response at different stages of HIV-1 infection.MethodsA5254 was a multicenter, cross-sectional study in people with HIV (PWH) recruited into 4 strata based on CD4 count and levels of plasma viremia: stratum (St) A: CD4 ≤200 cells/mm3, HIV-1 RNA (viral load [VL]) >1000 cps/mL; St B: CD4 ≤200, VL ≤1000; St C: CD4 >200, VL >1000; St D: CD4 >200, VL ≤1000. Oral/throat washings were obtained from all participants. Soluble markers were tested in oral/throat washings using a multibead fluorescent platform and were compared across strata. Linear regression was used to determine the associations between cytokines and HIV-1 in plasma and oral fluid.ResultsSt A participants had higher levels of interleukin (IL)-1β, IL-6, IL-17, tumor necrosis factor alpha (TNFα), and interferon gamma (IFNγ) compared with St B and D (P = .02; P < .0001) but were not different from St C. IL-8, IL-10, and IL-12 were elevated in St A compared with the other 3 strata (P = .046; P < .0001). Linear regression demonstrated that oral HIV-1 levels were associated with IL-1β, IL-6, IL-8, and TNFα production (R > .40; P < .001) when controlling for CD4 count and opportunistic infections.ConclusionsOur results show that high levels of oral HIV-1, rather than low CD4 counts, were linked to the production of oral immune mediators. Participants with AIDS and uncontrolled viremia demonstrated higher levels of pro- and anti-inflammatory soluble immune mediators compared with participants with lower HIV-1 RNA. The interplay of HIV-1 and these immune mediators could be important in the oral health of PWH

Meta-Analysis of DNA Tumor-Viral Integration Site Selection Indicates a Role for Repeats, Gene Expression and Epigenetics

Oncoviruses cause tremendous global cancer burden. For several DNA tumor viruses, human genome integration is consistently associated with cancer development. However, genomic features associated with tumor viral integration are poorly understood. We sought to define genomic determinants for 1897 loci prone to hosting human papillomavirus (HPV), hepatitis B virus (HBV) or Merkel cell polyomavirus (MCPyV). These were compared to HIV, whose enzyme-mediated integration is well understood. A comprehensive catalog of integration sites was constructed from the literature and experimentally-determined HPV integration sites. Features were scored in eight categories (genes, expression, open chromatin, histone modifications, methylation, protein binding, chromatin segmentation and repeats) and compared to random loci. Random forest models determined loci classification and feature selection. HPV and HBV integrants were not fragile site associated. MCPyV preferred integration near sensory perception genes. Unique signatures of integration-associated predictive genomic features were detected. Importantly, repeats, actively-transcribed regions and histone modifications were common tumor viral integration signatures

Detection and quantitation of HPV in genital and oral tissues and fluids by real time PCR

<p>Abstract</p> <p>Background</p> <p>Human papillomaviruses (HPVs) remain a serious world health problem due to their association with anogenital/oral cancers and warts. While over 100 HPV types have been identified, a subset is associated with malignancy. HPV16 and 18 are the most prevalent oncogenic types, while HPV6 and 11 are most commonly responsible for anogenital warts. While other quantitative PCR (qPCR) assays detect oncogenic HPV, there is no single tube assay distinguishing the most frequent oncogenic types and the most common types found in warts.</p> <p>Results</p> <p>A Sybr Green-based qPCR assay was developed utilizing degenerate primers to the highly conserved HPV E1 theoretically detecting any HPV type. A single tube multiplex qPCR assay was also developed using type-specific primer pairs and TaqMan probes that allowed for detection and quantitation of HPV6,11,16,18. Each HPV type was detected over a range from 2 × 10¹to 2 × 10⁶copies/reaction providing a reliable method of quantitating type-specific HPV in 140 anogenital/cutaneous/oral benign and malignant specimens. 35 oncogenic and low risk alpha genus HPV types were detected. Concordance was detected in previously typed specimens. Comparisons to the gold standard detected an overall sensitivity of 89% (95% CI: 77% - 96%) and specificity of 90% (95%CI: 52% - 98%).</p> <p>Conclusion</p> <p>There was good agreement between the ability of the qPCR assays described here to identify HPV types in malignancies previously typed using standard methods. These novel qPCR assays will allow rapid detection and quantitation of HPVs to assess their role in viral pathogenesis.</p

Detection and quantitation of HPV in anogenital and oral tissues and fluids of HIV-positive individuals by real-time PCR

Human papillomaviruses (HPV) remain a serious world health problem due to their association with anogenital and oral cancers and warts. While over 100 HPV types have been identified, only a subset is associated with malignancy. HPV16 and 18 are the most common oncogenic types, while HPV6 and 11 are the most common types responsible for anogenital warts. These four types cause up to 90% of HPV-associated disease. While other quantitative PCR (qPCR) assays can be used to detect oncogenic HPV, there is no single tube assay that distinguishes the most frequent oncogenic types and the most common types found in warts. A qPCR assay was developed that allowed for detection and quantitation of these 4 HPV types

Common Polymorphisms in IFI16 and AIM2 Genes Are Associated With Periodontal Disease

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142266/1/jper0663-sup-0009.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142266/2/jper0663-sup-0008.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142266/3/jper0663-sup-0010.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142266/4/jper0663-sup-0005.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142266/5/jper0663.pd