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

Salivary gland disease: a role for BK virus

Salivary gland disorders (SGD) cause significant morbidity but remain an enigma. SGD includes autoimmune disorder Sjogren's syndrome (SS), and a related HIV-associated salivary gland disease (HIV-SGD), that is AIDS defining in children and increasing in the adult population. Each of these maladies is characterized by loss of exocrine function resulting from chronic immune attack directed against the salivary glands with CD4+ (SS) or CD8+ (HIV-SGD) lymphocytic infiltrates within the gland tissue. The affected individuals are disfigured by facial asymmetry and 1-10% develop malignant lymphoproliferative disease. Further, the associated xerostomia instigates caries, mucosal pathology and periodontal disease. Despite progress made toward understanding aspects of SS, critical gaps remain in understanding the pathogenesis of SGD. The long term goal of this project is to make critical strides toward understanding the etiology of SGD in order to go beyond the ineffective palliative treatment that is currently the standard of care. 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 salivary gland disorders. BKV DNA and its gene products were consistently detected in HIV-SGD salivary gland biopsies and in a subset of SS patient. BKV was also detected in the peripheral blood and shed in oral fluids from HIV-SGD patients and not in control subjects. To confirm the in vivo findings an in vitro model was created whereby parotid and submandibular salivary gland cells were productively infected with BKV demonstrating each part of the viral life cycle. Salivary gland tropism was confirmed and the BKV receptor on salivary gland cells was defined. BKV transmission and pathogenesis is not well understood. Importantly, these studies suggest that BKV transmission may occur via the oral route. Differential gene expression studies were also performed on HIV-SGD salivary gland biopsies. Among the many modulated transcripts was a novel non-coding RNA, MALAT-1, that was highly up-regulated in the disease. Further investigation of this transcript revealed that BKV infection played an important role in its regulation and we report for the first time a mechanism for MALAT-1 regulation

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

The Association of Cytomegalovirus and Allostatic Load by Country of Birth and Length of Time in the United States

Background: Cytomegalovirus (CMV) is a highly prevalent virus with a worldwide distribution. It typically remains dormant in most individuals until reactivation. Immunocompromised states are known to be potential causes for CMV reactivation. Current research has shown a link in the decline of immigrant health among those living in the US for an extended period, though the impact of CMV on this is not clear. Methods: This study investigated the association between country of birth, duration of US residency, allostatic load, and latent cytomegalovirus infection (CMV IgG) in a sample of US adults aged 20–49. The data utilized for our analysis was obtained from the National Health and Nutrition Examination Survey (NHANES) conducted between 2001 and 2004. Allostatic load, an index measuring the cumulative physiological strain on the body as it strives to regain stability in the presence of chronic stress, provided a valuable approach to assess stress within the context of CMV exposure. Logistic regression modeling was employed to estimate odds ratios and confidence intervals for the analysis. The chi-square test of association and Cramer’s V statistic were used to assess the correlation among categorical variables, while Pearson’s correlation coefficient was applied to evaluate the relationship between continuous variables. The results revealed that individuals born outside the US and those with less than 20 years of residency in the US exhibited significantly higher proportions of positive CMV IgG compared to individuals born in the US. Specifically, individuals born outside the US had more than triple the odds of CMV IgG when adjusting for the AL index (OR = 3.69, p-value = 0.0063). A similar trend was observed when examining AL risk based on the duration of US residency. Furthermore, age and sex were identified as significant predictors (p-value < 0.05) of AL risk, considering the individual’s country of birth. In summary, the findings of this study significantly enhance our comprehension of the intricate interplay between cytomegalovirus (CMV) and allostatic load (AL). The investigation sheds light on how CMV and AL interact within specific demographic contexts, providing valuable insights into the underlying risk factors for CMV infection