Herpesvirus Infection Research Articles

A Single Center Retrospective Study on the Efficacy of Haploidentical Hematopoietic Stem Cell Transplantation in Patients with Myeloid Neoplasms over 50 Years Old

Objective: This study aims to evaluate the efficacy and safety of haploidentical hematopoietic stem cell transplantation in patients with myeloid neoplasms over 50 years old, and to compare the differences in survival, recurrence, and adverse reactions between patients aged 50-55 and over 55 years old. Methods: The patients with myeloid neoplasms over 50 years old who received haploidentical hematopoietic stem cell transplantation from November 2016 to December 2021 in the Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University, School of Medicine were enrolled. According to the age at the time of transplantation, patients were divided into Group A (50-55 years old) and Group B (≥ 55 years old). The differences in Overall survival (OS), progression free survival (PFS), non-relapse mortality (NRM), cumulative incidence of relapse (CIR), incidence of graft versus host disease (GVHD), and infection rate between the two groups were analyzed. Results: A total of 163 patients (group A, n=77; group B, n=86) were enrolled, including 112 cases of acute myeloid leukemia (AML), 39 cases of myelodysplastic neoplasms (MDS), 4 cases of chronic myeloid monocyte leukemia (CMML), 3 cases of primary myelofibrosis (MF), and 5 cases of chronic myeloid leukemia (CML). There were no statistically significant differences in baseline data between the two groups, including follow-up time, disease categories, HCT-CI score, remission status of AML patients, minimal residual lesion (MRD) level of AML patients, and IPSS-R score of MDS patients. However, more patients in Group A received myeloablative (MAC) conditioning than patients in Group B (92.2% vs 50%, P=0.000). The median follow-up time was 741 (7-2377) days. The overall 2-year OS is 73.0% ± 3.5%, 2-year PFS is 71.3% ± 3.6%, 2-year NRM is12.23%（7.65%-17.93%）, and 2-year CIR is 17.20%（11.64%-23.69%）. All patients in group A achieved hematopoietic reconstitution except one patient died of graft failure, while 5 patients of group B died of graft failure(P=0.126). Neutrophils and platelet reconstruction in Group B was slightly longer than in Group A. The neutrophils reconstruction occurred at a median of 12 (8-20) day and 13 (9-25) day, respectively (P=0.007), and platelet reconstruction occurred at a median of 12 (9-28) day and 13 (8-37) day, respectively (P=0.055). The 2-year OS of Group A and Group B was 76.6% ± 4.8% and 69.0 ± 5.1%, respectively (P=0.199); The 2-year PFS was 76.2% ± 4.9% and 66.9 ± 5.1%, respectively (P=0.236); The 2-year NRM was 9.16% (4.00% -16.96%) and 18.61% (11.18% -27.51%), respectively (P=0.094); The 2-year CIR was similar, with 14.66% (7.74% -23.67%) and 19.16% (11.48% -28.33%), respectively (P=0.782). Interestingly, there was a difference in NRM between patients receiving reduced-intensity (RIC) and MAC conditioning in Group B, which was 10.2% (3.69% -20.61%) and 25.58% (13.64% -39.34%), respectively (P=0.043), while there was no difference in CIR, which was 17.31% (7.88% -29.80%) and 18.90% (8.71% -32.06%), respectively (P=0.933). It is suggested that in older patients, the strength of conditioning regimen has a greater impact on NMR. The incidence of grade 3-4 aGVHD within 100 days in all patients was 11.84% (7.31% -17.56%), and the incidence of 2-year intensive cGVHD was 8.19% (4.58% -13.14%). The incidence of grade 3-4 aGVHD within 100 days was similar between the two groups, with 9.46% (4.13% -17.46%) and 14.10% (7.46% -22.81%) (P=0.368), respectively. The 2-year intensive cGVHD was 8.07% (3.26% -15.72%) and 8.28% (3.62% -15.42%) (P=0.890), with similar incidence rates. The incidence of bacterial septicemia, pneumonia, invasive fungal infection, herpes virus and other infections were similar in both groups. Univariate and multivariate analysis both showed that 50-55 years old was an independent protective factor of OS (2.384 (1070-5.312), P=0.034) and GRFS (2.683 (1.181-6.094), P=0.018) in AML patients. Conclusion: Haploidentical hematopoietic stem cell transplantation is an effective and safe treatment for myeloid neoplasms over the age of 50. Compared with patients aged 50 to 55 years old, patients with myeloid neoplasms aged over 55 years old had similar efficacy and safety. The impact of MAC and RIC pretreatment on the prognosis of patients at different ages may be different. This retrospective study is limited in number and needs more cases and prospective cohort study to further verify.

Experimental verification and identifying biomarkers related to insomnia

IntroductionInsomnia is the most common form of sleep deprivation (SD) observed in clinics. Although there are differences between insomnia and SD, they have similar symptoms and the same animal model. Currently, there is a lack of microarray data on insomnia. Therefore, for now, we are going to apply the SD data to insomnia. Although many studies have explained the possible mechanisms associated with insomnia, no previous studies have considered the key genes associated with insomnia or the relationship between insomnia and immune cells. In this study, we analyzed the relationship between key genes and immune cells by identifying biomarkers for the diagnosis of insomnia. Next, we verified the efficacy of these biomarkers experimentally.MethodsFirst, we downloaded four microarrays (GSE11755, GSE12624, GSE28750, and GSE48080) from the Gene Expression Omnibus (GEO) database, which included data from 239 normal human blood samples and 365 blood specimens from patients with SD. Then, we analyzed two groups of differentially expressed genes (DEGs) and used Support Vector Machine Recursive Feature Elimination (SVM-RFE) analysis and the Least Absolute Shrinkage and Selection Operator (LASSO) regression model to investigate these key genes. Next, we used CIBERSORT to investigate the composition of 22 immune cell components of key genes in SD patients. Finally, the expression levels of key biomarkers in sleep-deprived patients were examined by quantitative real-time polymerase chain reaction (qRT-PCR).ResultsA total of 50 DEGs were identified: six genes were significantly upregulated, and 44 genes were significantly downregulated. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that Salmonella infection, NOD-like receptor (NLR) signaling pathway, Kaposi sarcoma-associated herpesvirus infection, and Th17 cell differentiation were significant. Based on machine learning, we identified C2CD2L, SPINT2, APOL3, PKNOX1, and A2M as key genes for SD; these were confirmed by receiver operating characteristic (ROC) analysis. Immune cell infiltration analysis showed that C2CD2L, SPINT2, APOL3, PKNOX1, and A2M were related in different degrees to regulatory T cells (Tregs), follicular T helper cells, CD8 cells, and other immune cells. The qRT-PCR experiments confirmed that the expression levels of C2CD2L concurred with the results derived from machine learning, but PKNOX1 and APOL3 did not.DiscussionIn summary, we identified a key gene (C2CD2L) that may facilitate the development of biomarkers for insomnia.

Herpes Virus Infection in Lung Transplantation: Diagnosis, Treatment and Prevention Strategies.

Lung transplantation is an ultimate treatment option for some end-stage lung diseases; due to the intense immunosuppression needed to reduce the risk of developing acute and chronic allograft failure, infectious complications are highly incident. Viral infections represent nearly 30% of all infectious complications, with herpes viruses playing an important role in the development of acute and chronic diseases. Among them, cytomegalovirus (CMV) is a major cause of morbidity and mortality, being associated with an increased risk of chronic lung allograft failure. Epstein-Barr virus (EBV) is associated with transformation of infected B cells with the development of post-transplantation lymphoproliferative disorders (PTLDs). Similarly, herpes simplex virus (HSV), varicella zoster virus and human herpesviruses 6 and 7 can also be responsible for acute manifestations in lung transplant patients. During these last years, new, highly sensitive and specific diagnostic tests have been developed, and preventive and prophylactic strategies have been studied aiming to reduce and prevent the incidence of these viral infections. In this narrative review, we explore epidemiology, diagnosis and treatment options for more frequent herpes virus infections in lung transplant patients.

Cell Intrinsic Determinants of Alpha Herpesvirus Latency and Pathogenesis in the Nervous System.

Alpha herpesvirus infections (α-HVs) are widespread, affecting more than 70% of the adult human population. Typically, the infections start in the mucosal epithelia, from which the viral particles invade the axons of the peripheral nervous system. In the nuclei of the peripheral ganglia, α-HVs establish a lifelong latency and eventually undergo multiple reactivation cycles. Upon reactivation, viral progeny can move into the nerves, back out toward the periphery where they entered the organism, or they can move toward the central nervous system (CNS). This latency-reactivation cycle is remarkably well controlled by the intricate actions of the intrinsic and innate immune responses of the host, and finely counteracted by the viral proteins in an effort to co-exist in the population. If this yin-yang- or Nash-equilibrium-like balance state is broken due to immune suppression or genetic mutations in the host response factors particularly in the CNS, or the presence of other pathogenic stimuli, α-HV reactivations might lead to life-threatening pathologies. In this review, we will summarize the molecular virus-host interactions starting from mucosal epithelia infections leading to the establishment of latency in the PNS and to possible CNS invasion by α-HVs, highlighting the pathologies associated with uncontrolled virus replication in the NS.

CHRONIC RHINITIS IN CAT

A rescue female cat named Hanji aged 2 years with a body weight of 2.3 kg was examined at the Veterinary Internal Medicine Laboratory, Faculty of Veterinary Medicine, Udayana University. The purpose of the study was to diagnose, treat and evaluate the success of therapy in a case cat. Based on anamnesis, the cat had recurrent sneezing and nasal discharge and the cat had experienced eye pain so that the cat's left eye was broken and lost. On physical examination, there were oozing spots on both nostrils, sneezing and oozing. On palpation the right and left lymphonoduses were swollen, and on auscultation of the lungs there was stridor or abnormal lung sounds in general. Skin and nails, limbs, musculoskeletal, circulation, nerves, urogenital, and mucosa were normal. Supporting examination by conducting hematological examination, test kit, and isolation of bacterial and fungal identification. The test kit results showed that the case cat was negative for calicivirus infection or rhinotracheitis. The case cat was diagnosed with chronic rhinitis with a prognosis of fausta from the series of examinations performed. The therapy given to the case cat consisted of anti-inflammatory methylprednisolone (4 mg preparation, given orally (PO) with ½ tab once a day for 5 days), antibiotic doxycycline (100 mg preparation, given PO once a day for 6 days with ¼ tab, and supportive therapy in the form of vitamins and feed supplementation. On the 8th day of therapy showed success in treating chronic rhinitis and the eyes had begun to dry out. After supporting examinations such as negative test kit results showed no other indications such as Feline Calicivirus (FCV) or Feline Herpesvirus (FHV) disease so that the case animal was diagnosed with chronic rhinitis due to Chlamydia felis infection. Advice to owners if there are animals experiencing similar symptoms, immediately take them to the veterinarian for treatment so that the infection does not continue and severe and always maintain animal hygiene and surroundings.

Overall avidity declines in TCR repertoires during latent CMV but not EBV infection.

The avidity of the T-cell receptor (TCR) for antigenic peptides presented by the MHC (pMHC) on cells is an essential parameter for efficient T cell-mediated immunity. Yet, whether the TCR-ligand avidity can drive the clonal evolution of virus antigen-specific CD8 T cells, and how this process is determined in latent Cytomegalovirus (CMV)- against Epstein-Barr virus (EBV)-mediated infection remains largely unknown. To address these issues, we quantified monomeric TCR-pMHC dissociation rates on CMV- and EBV-specific individual TCRαβ clonotypes and polyclonal CD8 T cell populations in healthy donors over a follow-up time of 15-18 years. The parameters involved during the long-term persistence of virus-specific T cell clonotypes were further evaluated by gene expression profiling, phenotype and functional analyses. Within CMV/pp65-specific T cell repertoires, a progressive contraction of clonotypes with high TCR-pMHC avidity and low CD8 binding dependency was observed, leading to an overall avidity decline during long-term antigen exposure. We identified a unique transcriptional signature preferentially expressed by high-avidity CMV/pp65-specific T cell clonotypes, including the inhibitory receptor LILRB1. Interestingly, T cell clonotypes of high-avidity showed higher LILRB1 expression than the low-avidity ones and LILRB1 blockade moderately increased T cell proliferation. Similar findings were made for CD8 T cell repertoires specific for the CMV/IE-1 epitope. There was a gradual in vivo loss of high-avidity T cells with time for both CMV specificities, corresponding to virus-specific CD8 T cells expressing enhanced LILRB1 levels. In sharp contrast, the EBV/BMFL1-specific T cell clonal composition and distribution, once established, displayed an exceptional stability, unrelated to TCR-pMHC binding avidity or LILRB1 expression. These findings reveal an overall long-term avidity decline of CMV- but not EBV-specific T cell clonal repertoires, highlighting the differing role played by TCR-ligand avidity over the course of these two latent herpesvirus infections. Our data further suggest that the inhibitor receptor LILRB1 potentially restricts the clonal expansion of high-avidity CMV-specific T cell clonotypes during latent infection. We propose that the mechanisms regulating the long-term outcome of CMV- and EBV-specific memory CD8 T cell clonotypes in humans are distinct.

Identification of hub genes and pathways associated with cellular senescence in diabetic foot ulcers via comprehensive transcriptome analysis.

This research aimed to find important genes and pathways related to cellular senescence (CS) in diabetic foot ulcers (DFU) and to estimate the possible pathways through which CS affects diabetic foot healing. The GSE80178 dataset was acquired from the Gene Expression Omnibus (GEO) database, containing six DFU and three diabetic foot skin (DFS) samples. The limma package was used to identify differentially expressed genes (DEGs). At the same time, DEGs associated with CS (CS-DEGs) were found using the CellAge database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted on the CS-DEGs. A protein-protein interaction (PPI) network was built using the String database, and the cytoHubba plug-in within Cytoscape helped identify hub genes. Lastly, the miRNA-TF-mRNA regulatory network for these hub genes was established. In total, 66 CS-DEGs were obtained. These genes mainly focus on CS, Kaposi sarcoma-associated herpesvirus infection and Toll-like receptor signalling pathway. Eight hub genes were identified to regulate cell senescence in DFU, including TP53, SRC, SIRT1, CCND1, EZH2, CXCL8, AR and CDK4. According to miRNA-TF-mRNA regulatory network, hsa-mir-132-3p/SIRT1/EZH2 axis is involved in senescence cell accumulation in DFU.

The impact of chronic herpes virus infection on the bone system in children

Herpes virus infections currently are urgent problem in infectology, pediatrics and therapy. The feature of these diseases is the possibility of direct and indirect effects of the virus on various organs and systems: immune, nervous, endocrine, bone, in children in particular. The aim of the work is to summarize and systematize the available data on the impact of the chronic herpes virus infection on the bone system in children. Materials and methods: analysis of relevant Russian and international literature was carried out. Results: chronic herpes virus infections have pathological effects on bone system, in particular they can increase the risk of osteoporosis. Herpes viruses are involved in the pathogenesis of systemic inflammatory diseases, such as rheumatoid arthritis. Bone complications of herpes virus infections are the relevant issues. More research is needed to understand these complications more deeply.

Ambiguity effects of recombinant interferon α2B in an in vitro experiment on the expression of nuclear factor NF-KB, IFNα’βR AND IFNγR (CD119) receptors of neutrophilic granulocytes of patients with chronic herpes virus infections

Introduction. Neutrophil granulocytes (NGs) and the interferons system (IFN) play a leading role in antiviral immune defense. At the same time, patients suffering from atypical chronic active herpes-viral infections (ACA-HVI) often have neutropenia and impaired induced IFN/ and IFN production. It is possible that these patients have various disorders of intracellular signaling at all stages of IFN/ synthesis by immune system cells, including NG, which leads to IFN/ deficiency. An adequate level of nuclear factor NF-kB expression has positive effects on synthesis of IFN/ in the last stages of signaling. The disturbances in the expression of NF-kB can lead to defects in the synthesis of IFN/.
 The aim: to clarify the features of nuclear factor NF-kB, membrane receptors IFN|R and IFNR (CD119) expression on NG of patients with AСA-HVI, with the subsequent assessment of the recombinant IFN2b (recIFN2b) effects on them in the experimental system in vitro.
 Materials and methods: 25 patients with ACA-HVI of both sexes aged 23-64 years were included in the main group of the study (MSG). In the complex of the study for the detection of herpes-viral infections: the method of serodiagnosis (ELISA), for the detection of the genome of viruses - PCR-RT. 407 blood samples were examined in the in vitro system. Flow cytofluorimetry was used to estimate the amount (%) of NG expressing NF-kB, IFN|R, IFNR, and their expression levels before and after incubation with recIFN2b. Adequate statistical methods were applied.
 Results: In patients suffering from ACA-HVI, a deficiency of induced IFN and IFN production was detected, due to a decrease in the expression density of nuclear factor NF-kB NG, as well as a violation of the expression of membrane receptors IFN|R, IFNR. RecIFN2b in the in vitro system had a mixed effect on the expression of NF-kB, IFN|R and IFNR NG.
 Conclusion: The deficiency of induced IFN and IFN production in patients with ACA-HVI is associated with variable changes in NF-kB, IFN|R and IFNR NG expression. RecIFN2b in the in vitro system has an ambiguous effect on altered expression of NF-kB, IFN/ and IFN NG, which appears to depend on the innate or adaptive nature of these disorders.

A case of Kaposi’s varicelliform eruption in a 4-month-old child

It is well known that herpesviruses are pantropic, hence herpetic infections are characterized by a diverse clinical pattern. Often one of the syndromes of various «herpetic nosologic forms» is the exanthema syndrome. Traditionally, this is a vesicular rash accompanying the infection caused by herpes simplex virus, which occupies a fairly limited area, but the rashes can be completely different in nature, quantity, and localization. The article discusses a relatively rare variant of herpetic infection, called: Kaposi’s varicelliform eruption (eczema herpeticum), or Kaposi–Juliusberg varioliform pustulosis, characterized by the severity of clinical manifestations, often an unfavorable outcome, diagnostic and therapeutic difficulties. Photo documents of the dynamics of the skin process and laboratory parameters against the background of antiviral therapy are presented.

T-cell immunity status of children with combined infection with SARS-CoV-2 and human herpesviruses

There is an opinion that COVID-19 may be the cause of the reactivation of herpesviruses. Purpose. To study the state of the cellular link of adaptive immunity in the combined course of herpesvirus infections and COVID-19, to describe the clinical and laboratory characteristics of such conditions. Material and methods. In 2022–2023 a cross-sectional study was conducted. 71 patients aged from 1 month to 16 years were selected. Inclusion criteria: presence of signs of acute respiratory disease associated with SARS-CoV-2 and/or mononucleosis-like syndrome associated with active herpesvirus infection. All patients underwent a standard laboratory examination, determined by nosology, and an additional assessment of the cellular link of adaptive immunity (CD3+, CD4+, CD8+, CD3+HLA-DR+, CD3- CD16+CD56+ and CD20+) on a flow cytometer using monoclonal antibodies. Results and conclusion. The clinical pattern of the combined course of herpesvirus infection and SARS-CoV-2 differs little from monoinfections. Only at the first encounter with the Epstein-Barr virus, lymphoproliferative syndrome and hepatomegaly were more often recorded (p<0.05). Comparing the nature of the cellular immune response in patients with COVID-19 and herpesvirus infection, we observed pronounced differences. In patients with primary herpesvirus infection, the T-cell immune response was an order of magnitude higher than in acute COVID-19, herpesvirus reactivation, and co-infection, and this was true for all studied lymphocyte subpopulations. With SARS-CoV-2, a decrease in the total number of T-lymphocytes, T-helpers, and cytotoxic lymphocytes was observed. This condition, of course, cannot be called immunosuppression, but some parallel is clearly traced. And even with the combined course of SARS-CoV-2 and herpesvirus infection, the absolute values of T-cell immunity indicators do not reach the same indicators in patients without COVID-19. It is likely that this reason underlies the phenomenon of reactivation of persistent herpesviruses in patients infected with SARS-CoV-2.

Unveiling the mechanisms of nephrotoxicity caused by nephrotoxic compounds using toxicological network analysis

Billions of people worldwide have experienced irreversible kidney injuries, which is mainly attributed to the complexity of drug-induced nephrotoxicity. Consequently, there is an urgent need for uncovering the mechanisms of nephrotoxicity caused by compounds. In the present study, a network-based methodology was applied to explore the mechanisms of nephrotoxicity induced by specific compounds. Initially, a total of 42 nephrotoxic compounds and 60 kinds of syndromes associated with nephrotoxicity were collected from public resources. Afterwards, network localization and separation algorithms were employed to map the targets of compounds and diseases into the human interactome. By doing so, 199 statistically significant nephrotoxic networks displaying the interaction between compound targets and disease genes were obtained, which played pivotal roles in compounds-induced nephrotoxicity. Subsequently, enrichment analysis pinpointed core Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways that highlight commonalities in nephrotoxicity induced by nephrotoxic compounds. It was found that nephrotoxic compounds primarily induce nephrotoxicity by mediating the AGE-RAGE signaling pathway in diabetic complications, human cytomegalovirus infection, lipid and atherosclerosis, kaposi sarcoma-associated herpesvirus infection, apoptosis, and the PI3K-Akt pathways. These results provide valuable insights for preventing drug-induced nephrotoxicity. Furthermore, the employed approaches are also helpful to conduct research on other kinds of toxicities.

Ozone: An Adjunct in Dental Treatment.

Ozone is utilized in dentistry as ozonated oils, ozonated water, and gaseous ozone. The application of ozone in all specialties of dentistry has been demonstrated to be biocompatible. It has been demonstrated to encourage the remineralization of recently carious teeth, and it is utilized in dental caries and intracanal irrigants in endodontic treatment. Herpes virus infection, avascular osteonecrosis of the jaw, and alveolitis have all been treated with it. It can be applied as a supplement in the surgical and ongoing stages of periodontal disease and also hinders plaque formation. The purpose of the present review article is to discuss the numerous application of ozone in dentistry.

Incidence of Uveitis in Local Population of Lahore

Uveitis tends to afflict younger age groups than other eye disorders like cataract and glaucoma, which typically affect the elderly. The frequency and prevalence of infectious ocular inflammation may vary greatly depending on the etiological agent and geographical location. This study found that the most frequent causes of infectious uveitis, which can account for up to 20% of all cases of uveitis in the developed world, are toxoplasmosis and herpetic infection. We found out that uveitis was more prevalent in the female population and that too in the younger age group having anterior uveitis more common.

Clinical evaluation of antiviral combination treatment in cats with feline herpesvirus-1 infection

Clinical evaluation of antiviral combination treatment in cats with feline herpesvirus-1 infection

Impact of bovine herpesvirus-1 infection on fertility in dairy cattle

Bovine herpesvirus-1 (BoHV-1) is endemic in the UK dairy herd and can have an important negative impact on fertility. As well as being the cause of infectious pustular vulvovaginitis and infectious balanoposthitis, BoHV-1 can reduce conception rate following introduction of the virus in contaminated semen at the time of artificial insemination. Its ability to cause abortions, particularly in the last trimester, is well-documented and the incidence of abortions can be high following the introduction of infection to naïve herds. The impact of BoHV-1 on herd fertility will depend on the degree of herd immunity, route of infection and strain of BoHV-1. Vaccination has been shown to reduce spread of BoHV-1 within and between herds, and to significantly reduce the risk of abortion. In light of the cost of a single abortion, and the impact of BoHV-1 on milk yield, routine vaccination against BoHV-1 offers a cost-effective control strategy suitable for most UK dairy herds.

MiRNAs: Targets to Investigate Herpesvirus Infection Associated with Neurological Disorders.

Herpesvirus is associated with various neurological disorders and a specific diagnosis is associated with a better prognosis. MicroRNAs (miRNAs) are potential diagnostic and prognostic biomarkers of neurological diseases triggered by herpetic infection. In this review, we discuss miRNAs that have been associated with neurological disorders related to the action of herpesviruses. Human miRNAs and herpesvirus-encoded miRNAs were listed and discussed. This review article will be valuable in stimulating the search for new diagnostic and prognosis alternatives and understanding the role of these miRNAs in neurological diseases triggered by herpesviruses.

Hypoxia and HIF-1α promote lytic de novo KSHV infection.

The current view is that the default pathway of Kaposi's sarcoma-associated herpesvirus (KSHV) infection is the establishment of latency, which is a prerequisite for lifelong infection and viral oncogenesis. This view about KSHV infection is supported by the observations that KSHV latently infects most of the cell lines cultured in vitro in the absence of any environmental stresses that may occur in vivo. The goal of this study was to determine the effect of hypoxia, a natural stress stimulus, on primary KSHV infection. Our data indicate that hypoxia promotes euchromatin formation on the KSHV genome following infection and supports lytic de novo KSHV infection. We also discovered that hypoxia-inducible factor-1α is required and sufficient for allowing lytic KSHV infection. Based on our results, we propose that hypoxia promotes lytic de novo infection in cells that otherwise support latent infection under normoxia; that is, the environmental conditions can determine the outcome of KSHV primary infection.

Therapeutic Nucleic Acids against Herpes Simplex Viruses

The Herpes simplex virus (HSV) causes a wide range of diseases, ranging from relatively mild primary skin lesions to severe and often fatal episodes of encephalitis. Currently, the most effective drugs for HSV-infected people are nucleoside analogs (e.g., acyclovir) targeting enzymes encoded by viral DNA. The effectiveness of nucleoside analogs is reduced because of poor solubility in water, rapid intracellular catabolism, high cellular toxicity, and the appearance of resistant viral strains. Antisense technology that exploits nucleic acid fragments (NA-based agents) is a promising alternative to antiviral therapy due to the high affinity of these agents to target nucleic acids, their high solubility in water, and lower cellular toxicity. In the last decade, antisense oligonucleotides have been investigated as potential drugs for various diseases associated with “harmful” nucleic acids. Oligonucleotides with different chemical modifications targeted at specific regions of the HSV genome have shown effectiveness in suppressing the virus. siRNA-based agents have demonstrated prolonged and effective (up to 99%) inhibition of HSV replication. Based on the publications reviewed in the review over the past 30 years, it can be concluded about the prospects of using NA-based agents to combat herpes viral infections.

Hematopoietic stem cell transplantation and the noncytomegalovirus herpesviruses.

Although hematopoietic stem cell transplantation (HSCT) and other cellular therapies have significantly improved outcomes in the management of multiple hematological and nonhematological malignancies, the resulting impairment in humoral and cellular response increases the risk for opportunistic infection as an undesirable side effect. With their ability to establish latent infection and reactivate when the host immune system is at its weakest point, the Herpesviridae family constitutes a significant proportion of these opportunistic pathogens. Despite recent advancements in preventing and managing herpesvirus infections, they continue to be a common cause of significant morbidity and mortality in transplanted patients. Herein, we aim to provide and update on herpesvirus other than cytomegalovirus (CMV) affecting recipients of HSCT and other cellular therapies.