An HIV-induced mechanism for T cell quiescence and proviral latency

HIV persists in infected individuals despite effective antiretroviral therapy due to the rapid establishment of a latent HIV reservoir, mainly composed of quiescent memory CD4+ T cells1–3. The mechanisms governing the formation of the latent reservoir remain poorly understood. It is commonly assumed that entry of HIV into latency is a rare and random event associated with sporadic infection of effector T-cells transitioning to a memory phenotype4–8. Using human primary CD4+ T cell models, we show instead, that HIV infection itself triggers a strong transcriptomic remodeling that results in activation of a quiescence program, including downregulation of cellular proliferation and metabolic pathways. This transcriptional program is initiated by KLF2, a key regulator of quiescence, along with activation of the p53 pathway and downregulation of MYC. Loss and gain of function studies confirmed that KLF2 and p53 signaling are responsible for the downregulation of MYC and proliferation pathways, and consequently, proviral transcriptional silencing. Thus, HIV infection per se, enhances the formation of the latent reservoir in T-cells, ensuring viral persistence in infected individuals. These findings identify a new and unexpected mechanism for the formation of the latent HIV reservoir, and broaden the repertoire of strategies through which viruses can control the host cell to their advantage.

Temporal changes in mental response and prevention patterns, and their impact from uncertainty stress during the transition in China from the COVID-19 epidemic to sporadic infection

Objective: This prospective observational study examined changing trends of mental responses and prevention patterns, and their impact from uncertainty stress during the transition in China from the COVID 19 epidemic to sporadic infection. Setting: A prospective longitudinal observation design was utilized in this study. Participants: We recruited participants for an online panel survey from chat groups on Chinese social media platforms. Data collection: There were 7 waves of interviews. Data were obtained by an online survey. A special administrative WeChat group was established to manage the follow up data collection. Measures: Several mental responses and prevention patterns were each measured by single questionnaire items. Uncertainty stress was measured by 5-point scale. An irrational beliefs about prevention variable was comprised 5 common misconceptions, which manifested during the COVID 19 epidemic in China. Analysis: Sixty two participants completed all observation points and were included in the study. The Mann Kendall Test was used to assess changing trends across the seven observation points. The nonparametric linear mixed effects model was used to examine the association between uncertainty stress and mental and behavioral responses. Results: The mean uncertainty stress did not change significantly over the observation period (T:-0.911, P>0.05). This trend was also true for perceived risk (T: -0.141, P>0.05), perceived severity (T: 1.010, P>0.05), self efficacy for prevention (T: 0.129, P>0.05), and prevention behavior (T: 0.728, P>0.05). There was a statistically significant downwards trend in irrational beliefs about prevention (T: -4.993, p < 0.01), sleep (T: -2.499, p < 0.05), emotions (T: -5.650, p < 0.01), and lifestyle (T: -5.978, p < 0.01). The results showed that uncertainty stress was positively associated with irrational beliefs (beta: 0.16298, p<0.01). The more uncertainty stress, the worse was their sleep (beta: 0.02070, p<0.05), emotions (beta: 0.03462, p<0.01), and lifestyle(beta: 0.02056, p<0.05). High levels of uncertainty stress was negatively associated with self-efficacy for prevention and prevention behavior, beta value was =-1.33210 (p<0.01) and -0.82742 (p<0.01), respectively. Conclusion: As the COVID-19 virus spreads around the globe, it is currently in epidemic status in some countries, in sporadic status in another countries, and it will eventually transition to sporadic infection status. This study provides new information on changing trends of mental responses and prevention patterns from the COVID-19 epidemic as the transition to a sporadic infection period takes place. These results may have important policy and disease prevention in post-epidemic times.

Integrated Nutritional Supports for Diabetic Patients during COVID-19 Infection: A Comprehensive Review

Background: Diabetes mellitus is an endocrine metabolic disorders, affects the major organs in human and comorbid with others. Besides, diabetic patients are more prone to various infectious diseases as well as COVID-19 sporadic infection which are highly risk for diabetes mellitus patients. To combat this infections and comorbid situations, an integrated balanced nutritional supportive could help in maintaining sound health and increase immunity for prevention and management of such type of viral infections. Objectives: While information regarding nutritional supports in COVID-19 pandemic in diabetic patients are not available, this review aimed to accumulate the evidence from previous publications where studied about nutrition-based supports or interventions for viral diseases with special emphasis on respiratory infections. Methods: For reviewing, searches are done for getting journal articles into Google Scholar, Pub Med/Medline, Database of Open Access Journal and Science Direct for relevant data and information. Results: Integrated nutritional supports of both macronutrients and micronutrients guidelines including home-based physical exercise schedule is summarizes in this comprehensive review for possible prevention and management of diabetic patients in COVID-19 infections. The immune boosting benefits of some vitamins, trace elements, nutraceuticals and probiotics in viral infections of diabetic patients are also included. Conclusion: There is an urgent need for healthy diet and integrated nutritional supports with home-based physical activities for diabetic patients during the self-isolation period of COVID-19 Infection.

Hepatitis E: a largely underestimated, emerging threat

Hepatitis E virus has two distinct clinical and epidemiological patterns based on the varying genotypes. Genotypes 3 and 4 cause widespread, sporadic infection in high-income countries and are emerging as the most common type of viral hepatitis in much of Europe. These infections carry significant morbidity and mortality in the growing numbers of immunosuppressed patients or in patients with established liver disease. Furthermore the growing extra-hepatic associations of the virus, including neurological and kidney injury, suggest that it may have been misnamed as a ‘hepatitis’ virus. This review explores current understanding of the epidemiology, virology and clinical presentations of hepatitis E infection and identifies vulnerable patient groups, who are at serious risk from infection. Guidance is offered regarding the diagnosis, treatment and prevention of this growing public health hazard.

In VivoVirulence Characterization of Pregnancy-AssociatedListeria monocytogenesInfections

ABSTRACTListeria monocytogenesis a foodborne pathogen that infects the placenta and can cause pregnancy complications. Listeriosis usually occurs as a sporadic infection, but large outbreaks are also reported. Virulence from clinical isolates is rarely analyzed due to the large number of animals required, but this knowledge could help guide the response to an outbreak. We implemented a DNA barcode system using signature tags that allowed us to efficiently assay variations in virulence across a large number of isolates. We tested 77 signature-tagged clones of clinicalL. monocytogenesstrains from 72 infected human placentas and 5 immunocompromised patients, all of which were isolated since 2000. These strains were tested for virulence in a modified competition assay in comparison to that of the laboratory strain 10403S. We used twoin vivomodels of listeriosis: the nonpregnant mouse and the pregnant guinea pig. Strains that were frequently found at a high abundance within infected organs were considered hypervirulent, while strains frequently found at a low abundance were considered hypovirulent. Virulence split relatively evenly among hypovirulent strains, hypervirulent strains, and strains as virulent as 10403S. The laboratory strain was found to have an intermediate virulence phenotype, supporting its suitability for use in pathogenesis studies. Further, we found that splenic virulence and placental virulence are closely linked in both the guinea pig and mouse models. This suggests that outbreak and sporadic pregnancy-associatedL. monocytogenesstrains are not generally more virulent than lab reference strains. However, some strains did show consistent and reproducible virulence differences, suggesting that their further study may reveal deeper insights into the biological underpinnings of listeriosis.

Comparative genomic fingerprinting for the subtyping of Campylobacter jejuni and Campylobacter coli biotypes

Introduction/Objective. Thermophilic campylobacters, especially Campylobacter jejuni (C. jejuni) and Campylobacter coli (C. coli), are the most important causes of bacterial diarrhea in developed and developing countries. The disease can occur as a sporadic infection or as large and small outbreaks. Phenotyping and genotyping methods are in use to determine similarities between strains as well their possible common origin. The goal of the study was to compare discriminatory power of biotyping tests and comparative genomic fingerprinting (CGF) 40 (100%), as well as a combination of the two tests in detection of clonality or epidemiological relatedness between the studied strains. Methods. We investigated 23 Campylobacter strains using biotyping and CGF typing. Results. We found that biotyping was a more discriminatory method for C. coli, and CGF for C. jejuni strains. In the discrimination of C. jejuni strains, CGF had better discriminatory power [Simpson?s index of diversity (ID) was 0.879] over the discrimination of C. coli strains (Simpson?s ID was 0.389). Conclusion. Biotyping and CGF can be complementary methods in detection of similarity, relatedness and possible common origin between strains since the combination of biotyping and CGF methods gives more precise data about diversity within C. coli and C. jejuni strains.

Patterns of virulence factor expression and antimicrobial resistance in Achromobacter xylosoxidans and Achromobacter ruhlandii isolates from patients with cystic fibrosis

SUMMARYAchromobacter spp. are opportunistic pathogens increasingly recovered from adult patients with cystic fibrosis (CF). We report the characterization of 122 Achromobacter spp. isolates recovered from 39 CF patients by multilocus sequence typing, virulence traits, and susceptibility to antimicrobials. Two species, A. xylosoxidans (77%) and A. ruhlandii (23%) were identified. All isolates showed a similar biofilm formation ability, and a positive swimming phenotype. By contrast, 4·3% and 44·4% of A. xylosoxidans and A. ruhlandii, respectively, exhibited a negative swarming phenotype, making the swimming and swarming abilities of A. xylosoxidans significantly higher than those of A. ruhlandii. A. xylosoxidans isolates from an outbreak clone also exhibited significantly higher motility. Both species were generally susceptible to ceftazidime, ciprofloxacin, imipenem and trimethoprim/sulphamethoxazole and there was no significant difference in susceptibility between isolates from chronic or sporadic infection. However, A. xylosoxidans isolates from chronic and sporadic cases were significantly more resistant to imipenem and ceftazidime than isolates of the outbreak clone.

EPIZOOTOLOGICAL AND EPIDEMIOLOGICAL ZONING OF THE TERRITORY OF NORTH CAUCASUS FEDERAL REGION BY A DEGREE OF NON-WELFARE BY ANTHRAX USING ARC GIS10 PROGRAM

Aim. Conducting epizootological and epidemiological zoning ofthe territory of North Caucasus Federal Region (NCFR) by the degree of non-welfare by anthrax using Arc GIS10 program. Materials and methods. 2 parameters were used during zoning of the territories of subjects of NCFR (Stavropol Region, Karachaevo-Cherkessia, Kabardino-Balkaria, Chechen, North Ossetia-Alania, Ingushetia, Dagestan Republics) by non-welfare by anthrax: integrated parameter of infection risk and epizootics risk. The parameters were input into the Arc GIS10 program. Materials on infection of humans and animals with anthrax for the last 55 (1960 - 2014) years were used. Results. The regions of the territories of NCFR subjects were distributed by non-welfare degree into 4 groups: group 1 - regions with a low degree of non-welfare, group 2 - regions with an average degree of non-welfare, group 3 - regions with a high degree of non-welfare, group 4 - regions with a very high degree of non-welfare. Conclusion. Taking into account high parameters of spread and intensity of epizootological and epidemiological situation, regions of groups 3 and 4 could be classified as endemic territories for anthrax, whereas all the other regions could be attributed to the zone of sporadic infection manifestation.

Advances in Studies on Hepatitis E Virus

Hepatitis E virus (HEV) is transmitted mainly through food and water sources. HEV is a major public health problem faced by developing countries. HEV causes large outbreaks of hepatitis E (HE) or acute sporadic infection. HEV can also lead to chronic infection. HEV mainly affects the young, middle-aged people, and pregnant women, who especially display high rates of infection. This study reviews HE while considering its biological characteristics, clinical symptoms, epidemic characteristics, vaccine, and detection methods.