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While it is accepted that viruses can enter epithelial cells by endocytosis, the lack of an established biological mechanism for the trafficking of infectious virions through vaginal epithelial cells and their release from the plasma membrane has contributed to ongoing controversy about whether endocytosis is a mere artifact of some cell culture systems and whether squamous vaginal epithelial cells are even relevant as it pertains to HIV-1 transmission. In this study, we investigated the intracellular trafficking pathway that HIV-1 exploits to transcytose vaginal epithelial cells. The reduction of endosome tubulation by recycling endosome inhibitors blocked transcytosis of HIV-1 in a cell culture and transwell system. In addition, we demonstrate that although heat-inactivated virus was endocytosed as efficiently as native virus, heat-inactivated virus was trafficked exclusively to the lysosomal pathway for degradation following endocytosis. Lysosomal protease-specific inhibitors blocked the degradation of inactivated virions. Immunofluorescence analysis not only demonstrated that HIV-1 was inside the cells but the different colocalization pattern of native vs. heat inactivated virus with transferrin provided conclusive evidence that HIV-1 uses the recycling pathway to get across vaginal epithelial cells. Altogether, our findings demonstrate the precise intracellular trafficking pathway utilized by HIV-1 in epithelial cells, confirms that HIV-1 transcytosis through vaginal epithelial cells is a biological phenomenon and brings to light the differential intracellular trafficking of native vs heat-inactivated HIV-1 which with further exploration could prove to provide valuable insights that could be used in the prevention of transcytosis/transmission of HIV-1 across the mucosal epithelia.

Although most human immunodeficiency virus type 1 (HIV-1) cases worldwide are transmitted through mucosal surfaces, transmission through the oral mucosal surface is a rare event. More than 700 bacterial species have been detected in the oral cavity. Despite great efforts to discover oral inhibitors of HIV, little information is available concerning the anti-HIV activity of oral bacterial components. Here we show that a molecule from an oral commensal bacterium, Streptococcus cristatus CC5A can induce expression of APOBEC3G (A3G) and APOBEC3F (A3F) and inhibit HIV-1 replication in THP-1 cells. We show by qRT-PCR that expression levels of A3G and A3F increase in a dose-dependent manner in the presence of a CC5A extract, as does A3G protein levels by Western blot assay. In addition, when the human monocytic cell line THP-1 was treated with CC5A extract, the replication of HIV-1 IIIB was significantly suppressed compared with IIIB replication in untreated THP-1 cells. Knock down of A3G expression in THP-1 cells compromised the ability of CC5A to inhibit HIV-1 IIIB infectivity. Furthermore, SupT1 cells infected with virus produced from CC5A extract-treated THP-1 cells replicated virus with a higher G to A hypermutation rate (a known consequence of A3G activity) than virus used from untreated THP-1 cells. This suggests that S. cristatus CC5A contains a molecule that induces A3G/F expression and thereby inhibits HIV replication. These findings might lead to the discovery of a novel anti-HIV/AIDS therapeutic.

Background HIV-1 viral infectivity factor (Vif) is an essential accessory protein for HIV-1 replication. The predominant function of Vif is to counteract Apolipoprotein B mRNA-editing enzyme-catalytic polypeptide-like 3G (APOBEC3G, A3G), a potent host restriction factor that inhibits HIV-1 replication. Vif mediates the proteasomal degradation of A3G and inhibits A3G translation, thus diminishing the pool of A3G that is available to be packaged into budding virion. Although Vif is robust in degrading A3G, the protection provided against A3G is not absolute. Clinical and laboratory evidence have shown that A3G is not completely excluded from HIV-1 viral particles during HIV-1 replication. It remains unclear why the viral samples are still infectious when A3G has been packaged into the virions. Results In this study, we provide evidence that Vif continues to protect HIV-1 from the deleterious effects of A3G, even after packaging of A3G has occurred. When equal amounts of A3G were packaged into budding virions, the virus expressing functional Vif was more infectious and incurred fewer G to A hypermutations in the second round of infection compared to Vif-deficient virus. A Vif mutant with a defect in viral packaging showed a reduced ability to protect the HIV-1 genome from G to A hypermutations. Conclusion Our data suggest that even packaged A3G is still under the tyranny of Vif. Our work brings to light an additional caveat for any therapy that hopes to exploit the Vif-A3G axis. The ideal strategy would not only enhance A3G viral packaging, but also reduce HIV-1 Vif viral encapsidation.

Medroxyprogesterone acetate (MPA) is one of the most widely used contraceptives in the world. Epidemiologic studies have uncovered a possible link between the use of MPA and an increased risk of HIV-1 transmission. However, the understanding of the mechanism is still limited. Our previous publication demonstrated that the lysosomal activity in human vaginal epithelial cells attenuated the trafficking of viral particles during HIV-1 transcytosis. In this study, we show that treating human primary cervical epithelial cells with MPA led to a reduction in lysosomal activity. This reduction caused an increase in the intracellular HIV-1 accumulation and, consequently, an increase in viral release. Our study uncovers a novel mechanism by which MPA enhances HIV-1 release in primary cervical epithelial cells, thus providing vital information for HIV intervention and prevention.

A growing body of research seeks to conceptualize race as a multi-dimensional construct, attempting to move beyond a dummy variable approach to study social disparities. This research uses ‘socially-assigned race’, ‘ascribed race’, or ‘what race others think you are’ as opposed to self-identified race to assess self-rated health status among a representative study of the Latino population (n = 1,200). Our analysis shows how important the lived experience of Latinos and Hispanics (as measured by ascribed race and a host of control variables, including nativity and national origin) is on self-reported health. Using a series of logistic regressions, we find support for the ‘white advantage’ in Latino health status that is suggested in the literature, but this finding is sensitive to nativity, citizenship, and national origin. This research informs the study of racial and ethnic disparities, providing a detailed explanation for the ‘white health advantage’ finding within the socially-assigned race and health disparities literature.

Objectives: The objectives of our study were to determine the prevalence of major depressive symptoms and identify factors that are associated with major depressive symptoms among Black men with prostate cancer (PCa). Design: This study consisted of 415 Black men aged 40-81 years that entered the North Carolina Central Cancer Registry during the years 2007-2008. The primary outcome variable was depressive symptoms (CES-D). Factors included age, income, education, insurance status, treatment received, time between diagnosis and treatment, Gleason score, medical mistrust and experience with racism/discrimination. Logistic regression models were used to assess factors associated with the odds of having major depressive symptoms. Results: The prevalence of major depressive symptoms (≥16 on CES-D) among our sample of Black men with PCa was approximately 33%. Approximately 15% of the study participants underwent radiation beam treatment. Age was significantly associated with the odds of reporting major depressive symptoms (OR= .95, CI .91-.99) among Black men. In addition, compared with all other forms of treatment, Black men who underwent radiation beam treatment had higher odds (OR=2.38, CI 1.02- 5.51) of reporting major depressive symptoms. Conclusion: Nearly one-third of Black men with PCa in this study reported major depressive symptoms. Clinicians should pay closer attention to the mental health status of Black men with PCa, especially those who are younger and those who have undergone radiation beam treatment. Cancer survivorship, particularly quality of life, may be enhanced by opportunities for assessment, evaluation and intervention of depressive symptoms among these men disproportionately affected by PCa.Ethn Dis. 2017;27(4);429-436; doi:10.18865/ ed.27.4.429 

The objective of this study is to examine factors among a group of African American and White men in North Carolina and their assessment of prostate cancer treatment choice or belief that treatment chosen was best. A sample of men ( N  = 877) with a history of prostate cancer diagnosis was recruited from the North Carolina Cancer Registry during 2007–2008 and asked to participate in a telephone interview covering several measures about their initial prostate cancer treatment. Logistic regression was used to assess demographic, psychosocial, and clinical factors on whether they felt that they had chosen the best treatment for the disease. Respondents were majority White (52.7 %), married (75.9 %), and had surgery (67.9 %) as their initial treatment. At the bivariate level, factors associated with the belief that the treatment chosen was best were as follows: White race/ethnicity, higher levels of education, a more recent treatment date, having health insurance coverage, type of treatment received, higher levels of bother from side effects, greater contentment with their quality of life, and doctor discussions of the various treatment options. Similarly, the multivariate analysis showed increased odds of belief that the treatment chosen was the best among demographic (i.e., race/ethnicity, level of education, and health insurance coverage) as well as psychosocial and clinical variables (i.e., greater bother from side effects, greater contentment with their quality of life, and initial treatment received). Results suggest that demographic, psychosocial, and clinical factors play an important role for men in assessing their treatment choices for prostate cancer.

Background While it is accepted that viruses can enter epithelial cells by endocytosis, the lack of an established biological mechanism for the trafficking of infectious virions through vaginal epithelial cells and their release from the plasma membrane has contributed to ongoing controversy about whether endocytosis is a mere artifact of some cell culture systems and whether squamous vaginal epithelial cells are even relevant as it pertains to HIV-1 transmission. Methodology/Principal Findings In this study, we investigated the intracellular trafficking pathway that HIV-1 exploits to transcytose vaginal epithelial cells. The reduction of endosome tubulation by recycling endosome inhibitors blocked transcytosis of HIV-1 in a cell culture and transwell system. In addition, we demonstrate that although heat-inactivated virus was endocytosed as efficiently as native virus, heat-inactivated virus was trafficked exclusively to the lysosomal pathway for degradation following endocytosis. Lysosomal protease-specific inhibitors blocked the degradation of inactivated virions. Immunofluorescence analysis not only demonstrated that HIV-1 was inside the cells but the different colocalization pattern of native vs. heat inactivated virus with transferrin provided conclusive evidence that HIV-1 uses the recycling pathway to get across vaginal epithelial cells. Conclusions/Significance Altogether, our findings demonstrate the precise intracellular trafficking pathway utilized by HIV-1 in epithelial cells, confirms that HIV-1 transcytosis through vaginal epithelial cells is a biological phenomenon and brings to light the differential intracellular trafficking of native vs heat-inactivated HIV-1 which with further exploration could prove to provide valuable insights that could be used in the prevention of transcytosis/transmission of HIV-1 across the mucosal epithelia.

Although most human immunodeficiency virus type 1 (HIV-1) cases worldwide are transmitted through mucosal surfaces, transmission through the oral mucosal surface is a rare event. More than 700 bacterial species have been detected in the oral cavity. Despite great efforts to discover oral inhibitors of HIV, little information is available concerning the anti-HIV activity of oral bacterial components. Here we show that a molecule from an oral commensal bacterium, Streptococcus cristatus CC5A can induce expression of APOBEC3G (A3G) and APOBEC3F (A3F) and inhibit HIV-1 replication in THP-1 cells. We show by qRT-PCR that expression levels of A3G and A3F increase in a dose-dependent manner in the presence of a CC5A extract, as does A3G protein levels by Western blot assay. In addition, when the human monocytic cell line THP-1 was treated with CC5A extract, the replication of HIV-1 IIIB was significantly suppressed compared with IIIB replication in untreated THP-1 cells. Knock down of A3G expression in THP-1 cells compromised the ability of CC5A to inhibit HIV-1 IIIB infectivity. Furthermore, SupT1 cells infected with virus produced from CC5A extract-treated THP-1 cells replicated virus with a higher G to A hypermutation rate (a known consequence of A3G activity) than virus used from untreated THP-1 cells. This suggests that S. cristatus CC5A contains a molecule that induces A3G/F expression and thereby inhibits HIV replication. These findings might lead to the discovery of a novel anti-HIV/AIDS therapeutic.