Long-term Persistent Infection Research Articles

SARS-CoV-2 population dynamics in immunocompetent individuals in a closed transmission chain shows genomic diversity over the course of infection

BackgroundSARS-CoV-2 remains rapidly evolving, and many biologically important genomic substitutions/indels have characterised novel SARS-CoV-2 lineages, which have emerged during successive global waves of the pandemic. Worldwide genomic sequencing has been able to monitor these waves, track transmission clusters, and examine viral evolution in real time to help inform healthcare policy. One school of thought is that an apparent greater than average divergence in an emerging lineage from contemporary variants may require persistent infection, for example in an immunocompromised host. Due to the nature of the COVID-19 pandemic and sampling, there were few studies that examined the evolutionary trajectory of SARS-CoV-2 in healthy individuals.MethodsWe investigated viral evolutionary trends and participant symptomatology within a cluster of 16 SARS-CoV-2 infected, immunocompetent individuals with no co-morbidities in a closed transmission chain. Longitudinal nasopharyngeal swab sampling allowed characterisation of SARS-CoV-2 intra-host variation over time at both the dominant and minor genomic variant levels through Nimagen-Illumina sequencing.ResultsA change in viral lineage assignment was observed in individual infections; however, there was only one indel and no evidence of recombination over the period of an acute infection. Minor and dominant genomic modifications varied between participants, with some minor genomic modifications increasing in abundance to become the dominant viral sequence during infection.ConclusionsData from this cohort of SARS-CoV-2-infected participants demonstrated that long-term persistent infection in an immunocompromised host was not necessarily a prerequisite for generating a greater than average frequency of amino acid substitutions. Amino acid substitutions at both the dominant and minor genomic sequence level were observed in immunocompetent individuals during infection showing that viral lineage changes can occur generating viral diversity.

Microbial colonization of the nasal mucosa in the elderly with chronic rhinosinusitis

Objective: to study the bacteriological landscape of nasal secretions from the middle nasal passage in patients with chronic rhinosinusitis (CRS) aged 60 to 95 years and to identify the most significant genera and types of microorganisms characteristic of the treatment of chronic rhinosinusitis in this age group. Material and methods. Taking into account the inclusion and non-inclusion criteria, 83 patients were selected, of which the following groups were formed by age and presence of CRS: group 1 (comparison group 1) — patients without CRS aged 60-74 years (n=24); group 2 — (comparison group 2) patients without CRS aged 75-95 years (n=20); group 3 — patients with CRS aged 60-74 years (n=22) and group 4 — patients with CRS aged 75-95 years (n=18). All patients received swabs from the middle nasal passage. The obtained samples were sent for bacteriological examination to identify microorganisms. Results. The level of representatives of the genera Staphylococcus spp. with CRS in the elderly and senile 66.6 and 16.6%, respectively, Enterococcus spp. were seeded 66.6 and 16.6%. The presence of Klebsiella pneumoniae (16.6%), Klebsiella oxytoca (5.8%) and Pseudomonas aeruginosa (11.1%) indicates the risk of long-term persistent upper respiratory tract infections. In the group of patients with CRS aged 60-74, representatives of the genus Candidiales (5.5%) were seeded. Conclusion. S. aureus, S. haemolyticus and Enterococcus faecalis were the overwhelming species in elderly patients (60-74 years old). Microflora diversity in patients aged 75-95 years Klebsiella pneumoniae (16.6%), Klebsiella oxytoca (5.8%) and Pseudomonas aeruginosa (11.1 %) it affects the course and possible complications of CRS.

A Photo-induced Cross-Linking Enhanced A and B Combined Multi-Functional Spray Hydrogel Instantly Protects and Promotes of Irregular Dynamic Wound Healing.

Wounds in harsh environments can face long-term inflammation and persistent infection, which can slow healing. Wound spray is a product that can be rapidly applied to large and irregularly dynamic wounds, and can quickly form a protective film in situ to inhibit external environmental infection. In this study, a biodegradable A and B combined multi-functional spray hydrogel is developed with methacrylate-modified chitosan (CSMA1st) and ferulic acid (FA) as type A raw materials and oxidized Bletilla striata polysaccharide (OBSP) as type B raw materials. The precursor CSMA1st-FA/OBSP (CSOB-FA1st)hydrogelis formed by the self-cross-linking of dynamic Schiff base bonds, the CSMA-FA/OBSP (CSOB-FA)hydrogel is formedquickly after UV-vis light, so that the hydrogel fits with the wound. Rapid spraying and curing provide sufficient flexibility and rapidity for wounds and the hydrogel has good injectability, adhesive, and mechanical strength. In rats and miniature pigs, the A and B combined spray hydrogel can shrink wounds and promote healing of infected wounds, and promote the enrichment of fibrocyte populations. Therefore, the multifunctional spray hydrogel combined with A and B can protect irregular dynamic wounds, prevent wound infection and secondary injury, and be used for safe and effective wound treatment, which has a good prospect for development.

The fulminant form of pseudomembranous colitis in a child with cystic fibrosis

Аnnotation. A long-term persistent infection of the lower respiratory tract with cystic fibrosis and, as a consequence, the need for regular use of antibacterial drugs inevitably leads to changes in the composition of the intestinal microflora. At the same time, the most dangerous are toxigenic strains of Clostridium difficile. In turn, excessive growth of C. Difficile leads to increased sensitivity of enterocytes to its toxins. The leading pathogenicity factors of C. Difficile are exotoxins A (TcdA), B (TcdB) and binary toxin. TcdA and TcdB are enterotoxins acting on intestinal enterocytes, which leads to inflammation and necrosis of the mucous membrane. The binary toxin forms a complex on the enterocyte membrane that penetrates the cytoplasm, disrupts the functioning of the cell, leads to its death, and also enhances the adhesion and colonization of C. Difficile. One of the most accessible methods for determining the presence of toxin-producing C. Difficile in feces is immunochromatographic examination. The frequency of such a complication in patients with MV is unknown, the literature presents isolated cases of such a complication in Russia. There is one known case of fulminant pseudomembranous colitis (lethal). A clinical case of fulminant pseudomembranous colitis with recovery is presented. Conclusion. Patients with cystic fibrosis are at risk for the development of this complication, especially patients with a history of intestinal resection against the background of meconium ileus. In about 5% of cases, there is a fulminant course of pseudomembarnous colitis. In this form, the duration of the disease can be several hours. Lethality in the lightning-fast course reaches 58-70%. This option presents the greatest difficulty in terms of diagnosis due to atypical clinical symptoms. In particular, the diarrheal syndrome may not be pronounced or absent at all. Such patients often show symptoms of an acute abdomen, which makes differential diagnosis difficult. This is confirmed in our clinical case. It is necessary to increase awareness and alertness of doctors regarding the risk of developing this formidable complication in patients with Сystic fibrosis

Human Papillomavirus 16 Lineage A Variants Associated With Persistent Genital Infections in Men: The HPV Infection in Men (HIM) Study.

Human papillomavirus (HPV) 16 non-A lineage variants have higher carcinogenic potential for cervical cancer. HPV-16 variants natural history among males is not established. We evaluated HPV-16 variants prevalence and persistence in the external genitalia of men enrolled in the prospective HPV Infection in Men (HIM) Study. The HIM Study included men from the United States, Brazil, and Mexico. HPV-16 variants were distinguished using polymerase chain reaction sequencing. The prevalence of HPV-16 variants was assessed, and associations with infection persistence were estimated. We characterized the HPV-16 variants for 1700 genital swab samples from 753 men and 22 external genital lesions in 17 men. The prevalence of HPV-16 lineages differed by country and marital status (P < .001). Overall, 90.9% of participants harbored lineage A variants. The prevalence of non-A lineages was heterogenous among countries. HPV-16 lineage A variants were associated with a 2.69-fold increased risk of long-term persistent infections compared with non-A lineages. All high-grade penile intraepithelial neoplasia harbored lineage A variants and occurred in the context of long-term persistent infections with the same variants. The prevalence and persistence of HPV-16 variants observed at the male external genitalia suggest differences in the natural history of these variants between men and women, which may be associated with intrinsic differences in the infected genital epithelia.

Molecular mechanisms of stress-induced reactivation in mumps virus condensates

Negative-stranded RNA viruses can establish long-term persistent infection in the form of large intracellular inclusions in the human host and cause chronic diseases. Here, we uncover how cellular stress disrupts the metastable host-virus equilibrium in persistent infection and induces viral replication in a culture model of mumps virus. Using a combination of cell biology, whole-cell proteomics, and cryo-electron tomography, we show that persistent viral replication factories are dynamic condensates and identify the largely disordered viral phosphoprotein as a driver of their assembly. Upon stress, increased phosphorylation of the phosphoprotein at its interaction interface with the viral polymerase coincides with the formation of a stable replication complex. By obtaining atomic models for the authentic mumps virus nucleocapsid, we elucidate a concomitant conformational change that exposes the viral genome to its replication machinery. These events constitute a stress-mediated switch within viral condensates that provide an environment to support upregulation of viral replication.

Кистозно-железистая метаплазия мочевого пузыря.

Introduction. Cystic-glandular cystitis is one of the varieties of metaplasia of the bladder wall, which, in rare cases, can manifest itself in the form of voluminous polypoid growths. Clinical study. This article presents a case of polypoid changes in the bladder wall due to cystic glandular cystitis in a 74-year-old man against the background of a chronic inflammatory process and achalasia of the upper urinary tract. This observation confirms the theory of the etiological significance for the development of urothelial metaplasia of a long-term persistent urinary tract infection. The only reliable method for diagnosing cystic glandular cystitis and differential diagnosis of pseudotumor changes from urothelial carcinoma is morphological, after transurethral resection. Conclusion. The observation presented in this article showed that the clinical manifestations of cystic glandular cystitis can be variable and require an integrated approach to diagnosis and treatment.

Analysis of the causes of long-standing pelvic anterior sacral space infection and discussion of management techniques

Objective: To investigate the causes and management of long-term persistent pelvic presacral space infection. Methods: Clinical data of 10 patients with persistent presacral infection admitted to the Cancer Hospital of Zhengzhou University from October 2015 to October 2020 were collected. Different surgical approaches were used to treat the presacral infection according to the patients' initial surgical procedures. Results: Among the 10 patients, there were 2 cases of presacral recurrent infection due to rectal leak after radiotherapy for cervical cancer, 3 cases of presacral recurrent infection due to rectal leak after radiotherapy for rectal cancer Dixons, and 5 cases of presacral recurrent infection of sinus tract after adjuvant radiotherapy for rectal cancer Miles. Of the 5 patients with leaky bowel, 4 had complete resection of the ruptured nonfunctional bowel and complete debridement of the presacral infection using an anterior transverse sacral incision with a large tipped omentum filling the presacral space; 1 had continuous drainage of the anal canal and complete debridement of the presacral infection using an anterior transverse sacral incision. 5 post-Miles patients all had debridement of the presacral infection using an anterior transverse sacral incision combined with an abdominal incision. The nine patients with healed presacral infection recovered from surgery in 26 to 210 days, with a median time of 55 days. Conclusions: Anterior sacral infections in patients with leaky gut are caused by residual bowel secretion of intestinal fluid into the anterior sacral space, and in post-Miles patients by residual anterior sacral foreign bodies. An anterior sacral caudal transverse arc incision combined with an abdominal incision is an effective surgical approach for complete debridement of anterior sacral recalcitrant infections.

Expression profile of miRNAs computationally predicted to target PDL-1 in cervical tissues of different histology groups.

Background: Human papilloma virus (HPV) is considered a successful pathogen as it has the ability to evade host immune responses and establish long-term persistent infection. It has been reported that programmed death ligand 1 (PDL-1) expression is correlated with HPV-positivity and is increased with lesion progression or tumor metastasis in cervical cancer. The expression of microRNAs (miRNAs) is often deregulated in cancer, and their potential targets are affected. Methods: RNA was extracted from formalin-fixed paraffin-embedded (FFPE) cervical samples of different histological types, previously typed for the presence of HPV. A specific quantitative polymerase chain reaction (qPCR) protocol with SYBR Green was used to check for the expression of four miRNAs that were computationally predicted to target PDL-1. Results and conclusion: hsa-miR-20a-5p and hsa-miR-106b-5p showed an expression increase with the severity of the lesions, while hsa-miR-125b-5p depicted a significant decrease in its expression in cancerous samples when compared to normal samples.

Enterovirus-Cardiomyocyte Interactions: Impact of Terminally Deleted Genomic RNAs on Viral and Host Functions.

Group B enteroviruses, including coxsackievirus B3 (CVB3), can persistently infect cardiac tissue and cause dilated cardiomyopathy. Persistence is linked to 5' terminal deletions of viral genomic RNAs that have been detected together with minor populations of full-length genomes in human infections. In this study, we explored the functions and interactions of the different viral RNA forms found in persistently infected patients and their putative role(s) in pathogenesis. Since enterovirus cardiac pathogenesis is linked to the viral proteinase 2A, we investigated the effect of different terminal genomic RNA deletions on 2A activity. We discovered that 5' terminal deletions in CVB3 genomic RNAs decreased the levels of 2A proteinase activity but could not abrogate it. Using newly generated viral reporters encoding nano-luciferase, we found that 5' terminal deletions resulted in decreased levels of viral protein and RNA synthesis in singly transfected cardiomyocyte cultures. Unexpectedly, when full-length and terminally deleted forms were cotransfected into cardiomyocytes, a cooperative interaction was observed, leading to increased viral RNA and protein production. However, when viral infections were carried out in cells harboring 5' terminally deleted CVB3 RNAs, a decrease in infectious particle production was observed. Our results provide a possible explanation for the necessity of full-length viral genomes during persistent infection, as they would stimulate efficient viral replication compared to that of the deleted genomes alone. To avoid high levels of viral particle production that would trigger cellular immune activation and host cell death, the terminally deleted RNA forms act to limit the production of viral particles, possibly as trans-dominant inhibitors. IMPORTANCE Enteroviruses like coxsackievirus B3 are able to initiate acute infections of cardiac tissue and, in some cases, to establish a long-term persistent infection that can lead to serious disease sequelae, including dilated cardiomyopathy. Previous studies have demonstrated the presence of 5' terminally deleted forms of enterovirus RNAs in heart tissues derived from patients with dilated cardiomyopathy. These deleted RNAs are found in association with very low levels of full-length enterovirus genomic RNAs, an interaction that may facilitate continued persistence while limiting virus particle production. Even in the absence of detectable infectious virus particle production, these deleted viral RNA forms express viral proteinases at levels capable of causing viral pathology. Our studies provide mechanistic insights into how full-length and deleted forms of enterovirus RNA cooperate to stimulate viral protein and RNA synthesis without stimulating infectious viral particle production. They also highlight the importance of targeting enteroviral proteinases to inhibit viral replication while at the same time limiting the long-term pathologies they trigger.

Photothermal Hydrogel Encapsulating Intelligently Bacteria-Capturing Bio-MOF for Infectious Wound Healing.

Chronic wounds are characterized by long-term inflammation and persistent infection, which make them difficult to heal. Therefore, an urgent desire is to develop a multifunctional wound dressing that can prevent wound infection and promote wound healing by creating a favorable microenvironment. In this study, a curcumin-based metal-organic framework (QCSMOF-Van), loaded with vancomycin and coated with quaternary ammonium salt chitosan (QCS), was prepared. Multifunctional composite hydrogels were conveniently synthesized by combining methacrylic anhydride modified gelatin and methacrylic anhydride modified oxidized sodium alginate with QCSMOF-Van through radical polymerization and Schiff base reaction. It is important to note that the QCSMOF-Van could capture bacteria through the positive charges on the surface of QCS. In this process, due to the synergistic effect of broad-spectrum antibacterial Zn2+ and vancomycin, the metabolism of bacteria was well inhibited, and the efficient capturing and rapid killing of bacteria were achieved. The QCSMOF-Van hydrogels could precisely regulate the balance of M1/M2 phenotypes of macrophages, thereby promoting the regeneration of nerves and blood vessels, which promotes the rapid healing of chronic wounds. This advanced cascade management strategy for tissue regeneration highlights the potential of multifunctional composite hydrogels in chronic wound dressings.

Murine Models of Chronic Viral Infections and Associated Cancers.

Viruses are now recognized as bona fide etiologic factors of human cancer. Carcinogenic viruses include Epstein– Barr virus (EBV), high-risk human papillomaviruses (HPVs), hepatitis B virus (HBV), hepatitis C virus (HCV), human T-cell leukemia virus type 1 (HTLV-1), human immunodeficiency virus type 1 (HIV-1, indirectly), and several candidate human cancer viruses. It is estimated that 15% of all human tumors worldwide are caused by viruses. Tumor viruses establish long-term persistent infections in humans, and cancer is an accidental side effect of viral replication strategies. Viruses are usually not complete carcinogens, supporting the concept that cancer results from the accumulation of multiple cooperating events, in which human cancer viruses display different, often opposing roles. The laboratory mouse Mus musculus is one of the best in vivo experimental systems for modeling human pathology, including viral infections and cancer. However, mice are unsusceptible to infection with the known carcinogenic viruses. Many murine models were developed to overcome this limitation and to address various aspects of virus-associated carcinogenesis, from tumors resulting from xenografts of human tissues and cells, including cancerous and virus infected, to genetically engineered mice susceptible to viral infections and associated cancer. The review considers the main existing models, analyzes their advantages and drawbacks, describes their applications, outlines the prospects of their further development.

A protective role of HTLV-1 gp46-specific neutralizing and antibody-dependent cellular cytotoxicity-inducing antibodies in progression to adult T-cell leukemia (ATL).

Human T-cell leukemia virus type-1 (HTLV-1) establishes a long-term persistent infection in humans and causes malignant T-cell leukemia, adult T-cell leukemia (ATL). HTLV-1-specific cytotoxic T lymphocytes have been suggested to play a major role in the immunosurveillance of HTLV-1-infected T cells. However, it remains unclear whether HTLV-1-specific functional antibodies are also involved in the host defense. To explore the role of antibodies in the course of HTLV-1 infection, we quantitated HTLV-1-specific neutralizing and antibody-dependent cellular cytotoxicity (ADCC)-inducing antibody levels in plasma from asymptomatic carriers (ACs) and ATL patients. The levels of neutralizing antibodies, as determined by a syncytium inhibition assay, were significantly lower in acute and chronic ATL patients than in ACs. The levels of ADCC-inducing activity were tested using an autologous pair of HTLV-1-producing cells and cultured natural killer (NK) cells, which showed that the ADCC-inducing activity of IgG at a concentration of 100 µg/ml was comparable between ACs and acute ATL patients. The anti-gp46 antibody IgG levels, determined by ELISA, correlated with those of the neutralizing and ADCC-inducing antibodies. In contrast, the proviral loads did not correlate with any of these antibody levels. NK cells and a monoclonal anti-gp46 antibody reduced the number of HTLV-1 Tax-expressing cells in cultured peripheral blood mononuclear cells from patients with aggressive ATL. These results suggest a protective role for HTLV-1 neutralizing and ADCC-inducing antibodies during the course of HTLV-1 infection.

Murine Models of Chronic Viral Infections and Associated Cancers

Viruses are now recognized as bona fide etiologic factors of human cancer. Carcinogenic viruses include Epstein-Barr virus (EBV), high-risk human papillomaviruses (HPVs), hepatitis B virus (HBV), hepatitis C virus (HCV), human T-cell leukemia virus type 1 (HTLV-1), human immunodeficiency virus type 1 (HIV-1, indirectly), and several candidate human cancer viruses. It is estimated that 15% of all human tumors worldwide are caused by viruses. Tumor viruses establish long-term persistent infections in humans, and cancer is an accidental side effect of viral replication strategies. Viruses are usually not complete carcinogens, supporting the concept that cancer results from the accumulation of multiple cooperating events, in which human cancer viruses display different, often opposing roles. The laboratory mouse Mus musculus is one of the best in vivo experimental systems for modeling human pathology, including viral infections and cancer. However, mice are unsusceptible to infection with the known carcinogenic viruses. Many murine models were developed to overcome this limitation and to address various aspects of virus-associated carcinogenesis, from tumors resulting from xenografts of human tissues and cells, including cancerous and virus infected, to genetically engineered mice susceptible to viral infections and associated cancer. The review considers the main existing models, analyzes their advantages and drawbacks, describes their applications, outlines the prospects of their further development.

Development of a TaqMan® Allelic Discrimination qPCR Assay for Rapid Detection of Equine CXCL16 Allelic Variants Associated With the Establishment of Long-Term Equine Arteritis Virus Carrier State in Stallions.

Equine arteritis virus (EAV) is the causative agent of equine viral arteritis (EVA), a respiratory, systemic, and reproductive disease of equids. Following natural infection, up to 70% of the infected stallions can remain persistently infected over 1 year (long-term persistent infection [LTPI]) and shed EAV in their semen. Thus, the LTP-infected stallions play a pivotal role in maintaining and perpetuating EAV in the equine population. Previous studies identified equine C-X-C motif chemokine ligand 16 (CXCL16) as a critical host cell factor determining LTPI in the stallion’s reproductive tract. Two alleles (CXCL16 S and CXCL16 r ) were identified in the equine population and correlated with the susceptibility or resistance of a CD3+ T cell subpopulation in peripheral blood to in vitro EAV infection, respectively. Interestingly, CXCL16 S has been linked to the establishment of LTPI in stallions, and thus, genotyping stallions based on CXCL16 S/r would allow identification of those at the highest risk of establishing LTPI. Thus, we developed a TaqMan® allelic discrimination qPCR assay for the genotyping of the equine CXCL16 gene based on the identification of a single nucleotide polymorphism in position 1,073 based on NCBI gene ID: 100061442 (or position 527 based on Ensembl: ENSECAG00000018406.2) located in exon 2. One hundred and sixty horses from four breeds were screened for the CD3+ T cell susceptibility phenotype to EAV infection by flow cytometry and subsequently sequenced to determine CXCL16 allelic composition. Genotyping by Sanger sequencing determined that all horses with the resistant CD3+ T cell phenotype were homozygous for CXCL16 r while horses with the susceptible CD3+ T cell phenotype carried at least one CXCL16 S allele or homozygous for CXCL16 S . In addition, genotypification with the TaqMan® allelic discrimination qPCR assay showed perfect agreement with Sanger sequencing and flow cytometric analysis. In conclusion, the new TaqMan® allelic discrimination genotyping qPCR assay can be used to screen prepubertal colts for the presence of the CXCL16 genotype. It is highly recommended that colts that carry the susceptible genotype (CXCL16 S/S or CXCL16 S/r ) are vaccinated against EAV after 6 months of age to prevent the establishment of LTPI carriers following possible natural infection with EAV.

Chemotherapy of hematological malignancies in patients with COVID-19

In the era of COVID-19, the chemotherapy of patients with hematological malignancies has become the cornerstone in hematology. Secondary immunodeficiency as a result of hemoblastosis, predisposes to a more severe course of coronavirus infection, and specific antitumor treatment only exacerbates patients immunodeficiency. Thus, there is a problem of conducting chemotherapy during the COVID-19 pandemic. At the moment, there are no unified recommendations for risk assessment and choice of treatment for patients with oncohematological diseases and concomitant coronavirus infection. In this article, we present a series of clinical cases of patients with hematological malignancies diagnosed with coronavirus infection at the onset of a hematological disease or after chemotherapy. Patients with long-term persistent coronavirus infection requiring specific anticancer treatment were allocated to a separate group. We hope that this article will help to set a vector for further research, as well as serve as a clear example of the clinical situations that a hematologist may face during the COVID-19 pandemic.

Ancient Evolutionary History of Human Papillomavirus Type 16, 18 and 58 Variants Prevalent Exclusively in Japan.

Human papillomavirus (HPV) is a sexually transmitted virus with an approximately 8-kilo base DNA genome, which establishes long-term persistent infection in anogenital tissues. High levels of genetic variations, including viral genotypes and intra-type variants, have been described for HPV genomes, together with geographical differences in the distribution of genotypes and variants. Here, by employing a maximum likelihood method, we performed phylogenetic analyses of the complete genome sequences of HPV16, HPV18 and HPV58 available from GenBank (n = 627, 146 and 157, respectively). We found several characteristic clusters that exclusively contain HPV genomes from Japan: two for HPV16 (sublineages A4 and A5), one for HPV18 (sublineage A1) and two for HPV58 (sublineages A1 and A2). Bayesian phylogenetic analyses of concatenated viral gene sequences showed that divergence of the most recent common ancestor of these Japan-specific clades was estimated to have occurred ~98,000 years before present (YBP) for HPV16 A4, ~39,000 YBP for HPV16 A5, ~38,000 YBP for HPV18 A1, ~26,000 for HPV58 A1 and ~25,000 YBP for HPV58 A2. This estimated timeframe for the divergence of the Japan-specific clades suggests that the introduction of these HPV variants into the Japanese archipelago dates back to at least ~25,000 YBP and provides a scenario of virus co-migration with ancestral Japanese populations from continental Asia during the Upper Paleolithic period.

The crafty opponent: the defense systems of Staphylococcus aureus and response measures.

Staphylococcus aureus is a serious threat to public health. S. aureus infection can cause acute or long-term persistent infections that are often resistant to antibiotics and are associated with high morbidity and death. Understanding the defensive systems of S. aureus can help clinicians make the best use of antimicrobial drugs and can also help with antimicrobial stewardship. The mechanisms and clinical implications of S. aureus defense systems, as well as potential response systems, were discussed in this study. Because resistance to all currently available antibiotics is unavoidable, new medicines are always being developed. Alternative techniques, such as anti-virulence and bacteriophage therapies, are being researched and may become major tools in the fight against staphylococcal infections in the future, in addition to the development of new small compounds that affect cell viability.

Past COVID-19 infection and feasibility of transcatheter aortic valve replacement in a patient with severe aortic stenosis (a clinical case study)

A fatal case of severe stenosis of the aortic orifice in a patient with not diagnosed in time, long-term persistent covid infection is presented. The patient was hospitalized to resolve the issue of surgical correction of the aortic stenosis. On admission, there were symptoms of circulatory failure at the level of 3–4 functional class according to NYHA and angina pectoris clinic. A detailed collection of anamnesis about the epidemiological environment and symptoms of pneumonia suffered in the fall of 2020 raised suspicions of its covid genesis. Subsequently, this assumption was confirmed by the data of laboratory, instrumental studies, as well as the results of the pathological and anatomical autopsy. The study of microslides showed signs of extensive vasculitis with thrombosis of small branches of the pulmonary artery and foci of pneumofibrosis of various degrees of prescription, which also testified in favor of the transferred covid infection. Taking into account the severity of the patient’s condition upon admission, it was not possible to perform emergency intervention on the aortic valve. After stabilization of the state and regression of the phenomena of circulatory failure, it was planned to simultaneously perform endovascular revascularization of the coronary valve bed and transcatheter aortic valve replacement. The planned surgical intervention failed. The immunosuppressive effect of the SARS-CoV-2 virus, apparently, led to the activation of autoflora and an increase in inflammation for nosocomial infection. Bilateral polysegmental bacterial pneumonia that joined during hospitalization, against the background of postcoid changes in the lung parenchyma, contributed to the development of acute coronary syndrome with ventricular arrhythmias. The patient died from acute cardiopulmonary failure. The article also presents ideas about the operational tactics of managing patients with aortic stenosis in a pandemic.

Latently KSHV-Infected Cells Promote Further Establishment of Latency upon Superinfection with KSHV.

Kaposi’s sarcoma-associated herpesvirus (KSHV) is a cancer-related virus which engages in two forms of infection: latent and lytic. Latent infection allows the virus to establish long-term persistent infection, whereas the lytic cycle is needed for the maintenance of the viral reservoir and for virus spread. By using recombinant KSHV viruses encoding mNeonGreen and mCherry fluorescent proteins, we show that various cell types that are latently-infected with KSHV can be superinfected, and that the new incoming viruses establish latent infection. Moreover, we show that latency establishment is enhanced in superinfected cells compared to primary infected ones. Further analysis revealed that cells that ectopically express the major latency protein of KSHV, LANA-1, prior to and during infection exhibit enhanced establishment of latency, but not cells expressing LANA-1 fragments. This observation supports the notion that the expression level of LANA-1 following infection determines the efficiency of latency establishment and avoids loss of viral genomes. These findings imply that a host can be infected with more than a single viral genome and that superinfection may support the maintenance of long-term latency.