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MBio Mar 2015Nipah virus and Hendra virus are emerging, highly pathogenic, zoonotic paramyxoviruses that belong to the genus Henipavirus. They infect humans as well as numerous...
UNLABELLED
Nipah virus and Hendra virus are emerging, highly pathogenic, zoonotic paramyxoviruses that belong to the genus Henipavirus. They infect humans as well as numerous mammalian species. Both viruses use ephrin-B2 and -B3 as cell entry receptors, and following initial entry into an organism, they are capable of rapid spread throughout the host. We have previously reported that Nipah virus can use another attachment receptor, different from its entry receptors, to bind to nonpermissive circulating leukocytes, thereby promoting viral dissemination within the host. Here, this attachment molecule was identified as heparan sulfate for both Nipah virus and Hendra virus. Cells devoid of heparan sulfate were not able to mediate henipavirus trans-infection and showed reduced permissivity to infection. Virus pseudotyped with Nipah virus glycoproteins bound heparan sulfate and heparin but no other glycosaminoglycans in a surface plasmon resonance assay. Furthermore, heparin was able to inhibit the interaction of the viruses with the heparan sulfate and to block cell-mediated trans-infection of henipaviruses. Moreover, heparin was shown to bind to ephrin-B3 and to restrain infection of permissive cells in vitro. Consequently, treatment with heparin devoid of anticoagulant activity improved the survival of Nipah virus-infected hamsters. Altogether, these results reveal heparan sulfate as a new attachment receptor for henipaviruses and as a potential therapeutic target for the development of novel approaches against these highly lethal infections.
IMPORTANCE
The Henipavirus genus includes two closely related, highly pathogenic paramyxoviruses, Nipah virus and Hendra virus, which cause elevated morbidity and mortality in animals and humans. Pathogenesis of both Nipah virus and Hendra virus infection is poorly understood, and efficient antiviral treatment is still missing. Here, we identified heparan sulfate as a novel attachment receptor used by both viruses to bind host cells. We demonstrate that heparin was able to inhibit the interaction of the viruses with heparan sulfate and to block cell-mediated trans-infection of henipaviruses. Moreover, heparin also bound to the viral entry receptor and thereby restricted infection of permissive cells in vitro. Consequently, heparin treatment improved survival of Nipah virus-infected hamsters. These results uncover an important role of heparan sulfate in henipavirus infection and open novel perspectives for the development of heparan sulfate-targeting therapeutic approaches for these emerging infections.
Topics: Animals; Cells, Cultured; Cricetinae; Hendra Virus; Henipavirus Infections; Heparitin Sulfate; Humans; Leukocytes; Nipah Virus; Surface Plasmon Resonance; Survival Analysis; Virus Attachment
PubMed: 25759505
DOI: 10.1128/mBio.02427-14 -
MBio Dec 2022Human immunodeficiency virus type 1 (HIV-1) can integrate viral DNA into host cell chromosomes to establish a long-term stable latent reservoir, which is a major...
Human immunodeficiency virus type 1 (HIV-1) can integrate viral DNA into host cell chromosomes to establish a long-term stable latent reservoir, which is a major obstacle to cure HIV-1 infection. The characteristics of the HIV-1 latent reservoir have not been fully understood. Here, we identified 126 upregulated plasma membrane proteins in HIV-1 latently infected cells by a label-free liquid chromatography-tandem mass spectrometry analysis. The higher levels of CD98 expression in multiple HIV-1 latently infected cell lines and primary CD4 T cells compared to uninfected cells were further confirmed by quantitative reverse transcription PCR (RT-qPCR) and flow cytometry analyses. In addition, CD98 CD4 T cells displayed hyper-permissiveness to HIV-1 infection and possessed distinct immune phenotypic profiles associated with Th17 and peripheral follicular T helper (pTFH) characteristics. Notably, the CD98 resting memory CD4 T cells harbored significantly higher cell-associated viral RNA and intact provirus than CD98 counterparts in HIV-1-infected individuals receiving combined antiretroviral therapy. Furthermore, CD98 CD4 T cells exhibited a robust proliferative capacity and significantly contributed to the clonal expansion of the HIV-1 latent reservoir. Our study demonstrates that CD98 can be used as a novel biomarker of HIV-1 latently infected cells to indicate the effect of various strategies to reduce the viral reservoir. Identification of cellular biomarkers is the crucial challenge to eradicate the HIV-1 latent reservoir. In our study, we identified CD98 as a novel plasma membrane biomarker for HIV-1 permissiveness and latent infection. Importantly, CD98 CD4 T cells exhibited a hyper-permissiveness to HIV-1 infection and significantly contributed to the clonal expansion of the HIV-1 latent reservoir. CD98 could be targeted to develop therapeutic strategies to reduce the HIV-1 latent reservoir in further research.
Topics: Humans; Biomarkers; CD4-Positive T-Lymphocytes; HIV Infections; HIV-1; Latent Infection; Permissiveness; Virus Latency; Virus Replication; Fusion Regulatory Protein-1
PubMed: 36214569
DOI: 10.1128/mbio.02496-22 -
Substance Use & Misuse 2021Recent reports indicate that simultaneous alcohol and marijuana (SAM) use is a growing health concern among college students. As SAM use consists of both alcohol and...
Recent reports indicate that simultaneous alcohol and marijuana (SAM) use is a growing health concern among college students. As SAM use consists of both alcohol and marijuana, risk factors associated with either can serve as plausible targets by prevention efforts to reduce SAM use. : To explore this, the current study investigated the direct and indirect effects of two established risk factors for drinking on SAM use: perceived parental permissiveness toward drinking and friends' approval toward drinking (injunctive norms). : Incoming first-year students ( = 470) reported parental permissiveness, injunctive norms, alcohol use, and SAM use at baseline (T1) and 5 months later (T2). SAM use was assessed again 15 months post-baseline (T3). Path analysis was conducted to examine whether T2 variables mediated relationships between T1 variables and T3 SAM use. : Results revealed that T2 student alcohol use mediated the effects of T1 parental permissiveness, injunctive norms, and alcohol use on T3 SAM use. : Findings from this study extend research on SAM use by identifying perceived parental permissiveness and injunctive drinking norms as risk factors for SAM use through their effects on alcohol use. Based on these findings, it is plausible that parent-based interventions and interventions targeting peer injunctive norms during the first year of college could be used to effectively prevent or reduce SAM use.
Topics: Alcohol Drinking; Friends; Humans; Marijuana Smoking; Marijuana Use; Peer Group; Students; Universities
PubMed: 34596009
DOI: 10.1080/10826084.2021.1981390 -
Journal of Virology Apr 2018Measles is characterized by a transient immune suppression, leading to an increased risk of opportunistic infections. Measles virus (MV) infection of immune cells is...
Measles is characterized by a transient immune suppression, leading to an increased risk of opportunistic infections. Measles virus (MV) infection of immune cells is mediated by the cellular receptor CD150, expressed by subsets of lymphocytes, dendritic cells, macrophages, and thymocytes. Previous studies showed that human and nonhuman primate memory T cells express higher levels of CD150 than naive cells and are more susceptible to MV infection. However, limited information is available about the CD150 expression and relative susceptibility to MV infection of B-cell subsets. In this study, we assessed the susceptibility and permissiveness of naive and memory T- and B-cell subsets from human peripheral blood or tonsils to MV infection. Our study demonstrates that naive and memory B cells express CD150, but at lower frequencies than memory T cells. Nevertheless, both naive and memory B cells proved to be highly permissive to MV infection. Furthermore, we assessed the susceptibility and permissiveness of various functionally distinct T and B cells, such as helper T (T) cell subsets and IgG- and IgA-positive memory B cells, in peripheral blood and tonsils. We demonstrated that T1T17 cells and plasma and germinal center B cells were the subsets most susceptible and permissive to MV infection. Our study suggests that both naive and memory B cells, along with several other antigen-experienced lymphocytes, are important target cells of MV infection. Depletion of these cells potentially contributes to the pathogenesis of measles immune suppression. Measles is associated with immune suppression and is often complicated by bacterial pneumonia, otitis media, or gastroenteritis. Measles virus infects antigen-presenting cells and T and B cells, and depletion of these cells may contribute to lymphopenia and immune suppression. Measles has been associated with follicular exhaustion in lymphoid tissues in humans and nonhuman primates, emphasizing the importance of MV infection of B cells However, information on the relative susceptibility of B-cell subsets is scarce. Here, we compared the susceptibility and permissiveness to MV infection of human naive and memory T- and B-cell subsets isolated from peripheral blood or tonsils. Our results demonstrate that both naive and memory B cells are more permissive to MV infection than T cells. The highest infection levels were detected in plasma cells and germinal center B cells, suggesting that infection and depletion of these populations contribute to reduced host resistance.
Topics: Adult; B-Lymphocytes; Child; Female; Humans; Immunologic Memory; Male; Measles; Measles virus; Th1 Cells; Th17 Cells
PubMed: 29437964
DOI: 10.1128/JVI.00131-18 -
Pathogens (Basel, Switzerland) Nov 2021Viral encephalopathy and retinopathy caused by nervous necrosis virus (NNV), is one of the most threatening viral diseases affecting marine fish worldwide. In vitro...
Viral encephalopathy and retinopathy caused by nervous necrosis virus (NNV), is one of the most threatening viral diseases affecting marine fish worldwide. In vitro propagation of NNV strains is essential for the design of effective control measures. In the present study we analysed both the susceptibility and the permissiveness of five fish cell lines (E-11, GF-1, SAF-1, DLB-1, and SaB-1) to three NNV strains (one RGNNV, one SJNNV, and one reassortant RGNNV/SJNNV). E-11 and DLB-1 were demonstrated to be highly susceptible to NNV strains, with average adsorption efficiency (AE) values higher than 90%. SAF-1 also showed high susceptibility (AE 88%), whereas GF-1 can be regarded as moderately susceptible (AE around 50%). On the contrary, SaB-1 can be considered a poorly susceptible cell line (AE values below 20%). E-11 and GF-1 cell lines provided the highest production rates for RGNNV and RG/SJ (around 10) and both cell lines can be regarded as fully permissive for these viral types. However, the SJNNV production rate in GF-1 was only 17.8 and therefore this cell line should be considered semi-permissive for this genotype. In SAF-1 cells, moderate viral replication was recorded but differences in intracellular and extracellular production suggest that viral progeny was not efficiently released. In DLB-1 and SaB-1 the final viral titres obtained in E-11 were lower than those of the inoculum. However, RNA1 synthesis values seem to indicate that RGNNV replication in DLB-1 and SAF-1 could have been underestimated, probably due to a poor adaptation of the virus grown in these cell lines to E-11. Based on all these results, E-11 seems to be the most appropriate cell for in vitro culture of RGNNV, SJNNV, and reassortant strains.
PubMed: 34959520
DOI: 10.3390/pathogens10121565 -
Obesity Reviews : An Official Journal... Mar 2017Parenting style may be an important determinant of an individual's future weight status. However, reviews that evaluate the relationship between parenting style and... (Review)
Review
BACKGROUND
Parenting style may be an important determinant of an individual's future weight status. However, reviews that evaluate the relationship between parenting style and weight-related outcomes have not focused on prospective studies.
METHODS
We systematically searched PubMed, Embase and PsychInfo for studies published between 1995 and 2016 that evaluated the prospective relationship between parenting style experienced in childhood and subsequent weight outcomes.
RESULTS
We identified 11 prospective cohort studies. Among the eight studies that categorized parenting style into distinct groups (i.e. authoritative, authoritarian, permissive and neglectful), five provided evidence that authoritative parenting was associated with lower body mass index gains. Among the six highest quality studies, four suggested a protective role of authoritative parenting style against adverse weight-related outcomes. However, only one study controlled for a comprehensive set of confounders, and the small number of studies conducted within certain age groups precluded our ability to ascertain critical periods when parenting style is most strongly related to child weight.
CONCLUSIONS
The present literature supports the idea that authoritative parenting may be protective against later overweight and obesity, although findings are mixed. More prospective cohort studies of longer durations, with more sophisticated methods that examine age-varying relationships, and that control for a comprehensive set of confounders, are needed.
Topics: Authoritarianism; Body Mass Index; Body Weight; Databases, Factual; Humans; Obesity; Observational Studies as Topic; Overweight; Parent-Child Relations; Parenting; Parents; Permissiveness
PubMed: 28086262
DOI: 10.1111/obr.12497 -
Leukemia & Lymphoma Mar 2023To evaluate the impact of killer immunoglobulin-like receptor (KIR) genotyping in allogeneic hematopoietic stem cell transplantation for myeloid disorders at our...
To evaluate the impact of killer immunoglobulin-like receptor (KIR) genotyping in allogeneic hematopoietic stem cell transplantation for myeloid disorders at our institution, retrospective KIR genotyping was performed on 77 patients and their 10/10 matched unrelated donors. In a multivariate model including donor age, permissiveness, and presence of donor KIR B/x, an association with overall survival was observed ( = .047). Within the model, increasing donor age increased risk (RR 1.03 [1.00-1.06]/year, = .046), while donor KIR and permissiveness were not associated with risk (RR 0.51 [0.26-1.03] and RR 0.68 [0.34-1.36]). Grouping recipients by conditioning regimen or limiting the analysis to recipients of peripheral blood stem cells, no association between donor KIR and survival or relapse was identified. No significant associations were observed between overall survival, relapse, grade III-IV acute, or chronic graft versus host disease and presence of KIR B (B/x), quantity of donor KIR B haplotype motifs, or centromeric KIR type (all > .05).
Topics: Humans; Haplotypes; Unrelated Donors; Retrospective Studies; HLA Antigens; Hematopoietic Stem Cell Transplantation; Chronic Disease; Receptors, KIR; Graft vs Host Disease; Recurrence
PubMed: 36448323
DOI: 10.1080/10428194.2022.2151838 -
Scientific Reports Dec 2016The larval stages of malaria vector mosquitoes develop in water pools, feeding mostly on microorganisms and environmental detritus. Richness in the nutrient supply to...
The larval stages of malaria vector mosquitoes develop in water pools, feeding mostly on microorganisms and environmental detritus. Richness in the nutrient supply to larvae influences the development and metabolism of larvae and adults. Here, we investigated the effects of larval diet on the development, microbiota content and permissiveness to Plasmodium of Anopheles coluzzii. We tested three fish diets often used to rear mosquitoes in the laboratory, including two pelleted diets, Dr. Clarke's Pool Pellets and Nishikoi Fish Pellets, and one flaked diet, Tetramin Fish-Flakes. Larvae grow and develop faster and produce bigger adults when feeding on both types of pellets compared with flakes. This correlates with a higher microbiota load in pellet-fed larvae, in agreement with the known positive effect of the microbiota on mosquito development. Larval diet also significantly influences the prevalence and intensity of Plasmodium berghei infection in adults, whereby Nishikoi Fish Pellets-fed larvae develop into adults that are highly permissive to parasites and survive longer after infection. This correlates with a lower amount of Enterobacteriaceae in the midgut microbiota. Together, our results shed light on the influence of larval feeding on mosquito development, microbiota and vector competence; they also provide useful data for mosquito rearing.
Topics: Animal Feed; Animals; Anopheles; Larva; Plasmodium berghei
PubMed: 27910908
DOI: 10.1038/srep38230 -
Journal of Addictions Nursing 2016The United States is trending toward more permissiveness regarding recreational and medicinal marijuana (MJ). Many conditions for which MJ is recommended, prescribed, or...
The United States is trending toward more permissiveness regarding recreational and medicinal marijuana (MJ). Many conditions for which MJ is recommended, prescribed, or self-prescribed are symptoms that advanced practice nurses address daily. Yet, the silence of nursing scientists on ethics, practices, and policies regarding such clinical decisions is deafening. This is but one of many contradictions about MJ use that we discuss in this article. We do not propose to resolve these contradictions; that is left to the community of nurse scientists in interprofessional discourse. Collectively, we must explore these contradictions and, through evidence-based policy recommendations, overcome the silence about how providers view MJ, how it might be helpful, its risks, and cultural shifts that have accompanied a changed political/legal environment. Long term, we must close the gaps in the nursing knowledge base regarding MJ as it affects users and how it is used interventionally.
Topics: Humans; Medical Marijuana; Nurse Practitioners; Practice Patterns, Nurses'; United States
PubMed: 26950836
DOI: 10.1097/JAN.0000000000000105 -
Psychiatry Investigation Jun 2022Suicide is a complex phenomenon; therefore, it should be approached in light of sociocultural perspectives and the general attitude toward suicide. This study aimed to...
OBJECTIVE
Suicide is a complex phenomenon; therefore, it should be approached in light of sociocultural perspectives and the general attitude toward suicide. This study aimed to extract factors from the Attitude Toward Suicide Scale (ATTS) and investigate the relationship between attitudes toward suicide and suicidal behavior (i.e., suicidal idea, plan, and attempt) by using a representative sample of Korean adults.
METHODS
Three thousand Koreans aged 19 to 75 years were surveyed cross-sectionally in 2013 and 2018. The data collected were subjected to exploratory factor analysis. Extracted attitude factors were compared using a suicidal behavior continuum. Univariate and multivariate logistic models were constructed to compare the association between attitude factors and suicidal behaviors.
RESULTS
Among the participants, 477 (15.9%) experienced suicidal idea only, 85 (2.8%) had a suicidal plan without attempt, and 58 (1.9%) attempted suicide. Four meaningful factors were extracted from the factor analysis: "permissiveness," "unjustified behavior," "preventability/readiness to help," and "loneliness." "Permissiveness," "unjustified behavior," and "loneliness" factors showed significant trends across the suicidal behavior continuum. Permissive attitude toward suicide increased the odds of suicidal idea, suicidal plan, and suicide attempt (adjusted odds ratio [aOR]=1.49, 95% confidence interval [CI]=1.25-1.79; aOR=2.79, 95% CI=1.84-4.25; aOR=2.67, 95% CI=1.65-4.33), while attitude toward suicide as unjustified behavior decreased the odds of suicidal ideation and attempt (aOR=0.79, 95% CI=0.67-0.94; aOR=0.64, 95% CI=0.42-0.99).
CONCLUSION
A significant association was found between attitude toward suicide and suicidal behaviors. Attitude toward suicide is a modifiable factor that can be used to develop prevention policies.
PubMed: 35753681
DOI: 10.30773/pi.2021.0361