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Topic Review
Extrahepatic Replication of Hepatitis E Virus (HEV)
Hepatitis E virus (HEV) is an emerging viral disease known to cause acute viral hepatitis globally. Various genotypes of HEV have been identified that produce genotype specific lesions depending on the HEV targeted population. Extrahepatic existence of HEV was related to clinical manifestations via different case reports, case–control studies, and prospective studies. Knowledge about HEV-related extrahepatic diseases is very important for clinicians.
  • 701
  • 23 Mar 2023
Topic Review
Management of Cytomegalovirus Infections
Cytomegalovirus (CMV) infections may increase morbidity and mortality in immunocompromised patients. Until recently, standard antiviral drugs against CMV were limited to viral DNA polymerase inhibitors (val)ganciclovir, foscarnet and cidofovir with a risk for cross-resistance. These drugs may also cause serious side effects.
  • 698
  • 25 Jan 2024
Topic Review
Functions of Circular RNA
Circular RNAs (circRNAs) represent single-stranded RNA species that contain covalently closed 3′ and 5′ ends that provide them more stability than linear RNA, which has free ends. Emerging evidence indicates that circRNAs perform essential functions in many DNA viruses, including coronaviruses, Epstein–Barr viruses, cytomegalovirus, and Kaposi sarcoma viruses. Recent studies have confirmed that circRNAs are present in viruses, including DNA and RNA viruses, and play various important functions such as evading host immune response, disease pathogenesis, protein translation, miRNA sponges, regulating cell proliferation, and virus replication. Studies have confirmed that circRNAs can be biological signatures or pathological markers for autoimmune diseases, neurological diseases, and cancers. 
  • 697
  • 13 Jul 2023
Topic Review
Zika Virus in Brief
The Zika virus, a member of the Flaviviridae family, stands as a testament to the ever-evolving landscape of global health concerns in the early 21st century. In its nascent years, this virus inhabited the shadows of medical obscurity, inflicting sporadic, seemingly inconsequential bouts of mild illness primarily within the continents of Africa and Asia. Its existence remained relegated to the annals of medical journals and local health records, with little resonance in the broader global health discourse. However, this viral entity was destined for a meteoric rise to infamy, an emergence that would reverberate throughout the international community. The watershed moment transpired in 2015 when the Zika virus, once a modest player on the infectious disease stage, seized the spotlight by inciting a large-scale epidemic that unfurled across the vast expanse of the Americas. This sudden and dramatic expansion of the virus's reach thrust it into the forefront of global public health concerns, sending shockwaves through scientific, medical, and governmental circles. As we embark on this comprehensive review, it is essential to unravel the multifaceted tapestry of the Zika virus's journey. Beyond its mere identification and characterization, this exploration will delve deep into its enigmatic origins, intricate modes of transmission, the myriad impacts it has wrought upon human health, and the concerted efforts undertaken globally to wrest control from its insidious grip. This virus, once consigned to relative obscurity, has compelled the world's attention, ushering in a new era of infectious disease management and prompting a collective response from the global community. The story of the Zika virus serves as both a cautionary tale and a testament to the resilience and adaptability of pathogens in the face of a changing world.
  • 693
  • 28 Sep 2023
Topic Review
Unique Populations of Hepatitis C
Direct-acting antivirals (DAA), including RNA-dependent polymerase inhibitors (anti-NS5B), protease inhibitors (PI, anti-NS3/4A) and anti-NS5A inhibitors, have radically changed the landscape of patients with chronic hepatitis C virus (HCV) infection. The availability of DAA together with the improvement of worldwide access to treatment could potentially lead to HCV elimination by 2030 as endorsed by the World Health Organization (WHO). However, some patients have historically been part of the so-called unique or special populations. This term generally refers to those who are difficult-to-treat due to unreached sustained virological response (SVR), potential treatment side effects or drug interactions or co-morbidities.
  • 686
  • 21 Jun 2021
Topic Review
Immune Evasion by Betaherpesviruses
The human immune system boasts a diverse array of strategies for recognizing and eradicating invading pathogens. Human betaherpesviruses, a highly prevalent subfamily of viruses, include human cytomegalovirus (HCMV), human herpesvirus (HHV) 6A, HHV-6B, and HHV-7. These viruses have evolved numerous mechanisms for evading the host response. 
  • 682
  • 27 Oct 2021
Topic Review
COVID-19 and Global Monitoring&Surveillance
The spectrum of emerging new diseases as well as re-emerging old diseases is broadening as infectious agents evolve, adapt, and spread at enormous speeds in response to changing ecosystems. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a recent phenomenon and may take a while to understand its transmission routes from less travelled territories, ranging from fomite exposure routes to wastewater transmission. The critical challenge is how to negotiate with such catastrophic pandemics in high-income countries (HICs ~20% of the global population) and low-and middle-income countries (LMICs ~ 80% of the global population) with a total global population size of approximately eight billion, where practical mass testing and tracing is only a remote possibility, particularly in low-and middle-income countries (LMICs). Keeping in mind the population distribution disparities of high-income countries (HICs) and LMICs and urbanisation trends over recent years, traditional wastewater-based surveillance such as that used to combat polio may help in addressing this challenge. The COVID-19 era differs from any previous pandemics or global health challenges in the sense that there is a great deal of curiosity within the global community to find out everything about this virus, ranging from diagnostics, potential vaccines/therapeutics, and possible routes of transmission. In this regard, the fact that the gut is the common niche for both poliovirus and SARS-CoV-2, and due to the shedding of the virus through faecal material into sewerage systems, the need for long-term wastewater surveillance and developing early warning systems for better preparedness at local and global levels is increasingly apparent. 
  • 680
  • 23 Mar 2021
Topic Review
Transkingdom Analysis of the Female Reproductive Tract
The female reproductive tract (FRT) microbiome plays a vital role in maintaining vaginal health. Viruses are key regulators of other microbial ecosystems, but little is known about how the FRT viruses (virome), particularly bacteriophages that comprise the phageome, impact FRT health and dysbiosis. 
  • 680
  • 30 Mar 2022
Topic Review
Gut Reaction to SIV&SHIV Infection
SIV and SHIV-infected NHPs exhibit a range of viral burdens, pathologies, and responses to combinatorial antiretroviral therapy (cART) regimens and the choice of the NHP model for AIDS could influence outcomes in studies investigating interventions. Previously, in rhesus macaques (RMs) we showed that maintenance of mucosal Th17/Treg homeostasis during SIV infection correlated with a better virological response to cART. Here, in RMs we compared viral kinetics and dysregulation of gut homeostasis, defined by T cell subset disruption, during highly pathogenic SIVΔB670 compared to SHIV-1157ipd3N4 infection.SHIV infection resulted in lower acute viremia and less disruption to gut CD4 T-cell homeostasis. Additionally, 24/24 SHIV-infected versus 10/19 SIV-infected animals had sustained viral suppression <100 copies/mL of plasma after 5 months of cART. Significantly, the more profound viral suppression during cART in a subset of SIV and all SHIV-infected RMs corresponded with less gut immune dysregulation during acute SIV/SHIV infection, defined by maintenance of the Th17/Treg ratio. These results highlight significant differences in viral control during cART and gut dysregulation in NHP AIDS models and suggest that selection of a model may impact the evaluation of candidate therapeutic interventions for HIV treatment and cure strategies. 
  • 679
  • 26 Aug 2021
Topic Review
APOBECs and Virus Restriction
The apolipoprotein B mRNA editing enzyme, catalytic polypeptide (APOBEC) enzyme family in humans has 11 members with diverse functions in metabolism and immunity. The enzymes deaminate cytosine in RNA or single-stranded (ss) DNA, which forms uracil. The name is derived from the first discovered family member, APOBEC1, that edits the apolipoprotein B mRNA and other mRNAs. Uracil in RNA has a coding function, but in single-stranded (ss)DNA, it is promutagenic. Amazingly, these modification enzymes make cellular function and immunity better. For example, some family members purposefully induce these mutations in viral genomes to restrict their replication. However, events can sometimes go wrong, leading to inappropriate expression or activity, which can result in somatic mutations and cancer evolution. 
  • 674
  • 08 Oct 2021
Topic Review
Chronic Expression of Pro-Inflammatory Cytokines in Long COVID/PASC
Long COVID, also referred to as Post-Acute Sequelae of COVID (PASC), is probably triggered during SARS-CoV-2 infection and acute COVID-19 by SARS-CoV-2 Spike-protein binding and hyper-activating the cell-membrane expressed Receptor for Advance Glycation End-products (mRAGE) and Toll-Like Receptor 4 (TLR4). SARS-CoV-2 infects lung monocytes by Spike binding to mRAGE (not ACE2). During acute COVID-19, high levels of IL-6 hyper-stimulate S100A8/A9 expression and secretion. Although no viral protein nor mRNA can be detected in half of long COVID (PASC) patients, there is a significant elevation of serum levels of IL-1b, IL-6, TNFa, and S100A8/A9. It appears that a pathological pro-inflammatory feedback loop (the TLR4/RAGE-loop) is established during acute COVID-19, which is maintained by S100A8/A9 > RAGE/TLR4 chronic inflammatory signalling, even after SARS-CoV-2 has been cleared from the body. During long COVID/PASC, Ca2+-binding protein S100A8/A9 chronically stimulates TLR4/RAGE-signalling to induce chronic expression of IL-1b, IL-6 and TNFa. Secreted IL-6 binds to its IL-6R receptor on the surface of other cells and signals via STAT3 and C/EBPb for more S100A8/A9 expression. Secreted IL-1b binds to its receptor IL-1R on other cells, and signals via NFkB for more mRAGE and TLR4 expression. New S100A8/A9 can bind and activate cell-surface mRAGE and TLR4 to stimulate expression of more IL-1b, IL-6 and TNFa. This process establishes a pathogenic pro-inflammatory TLR4/RAGE-loop: IL-1b + IL-6 > IL-1R + IL-6R > TLR4/mRAGE + S100A8/A9 > IL-1b + IL-6, which generates multi-organ inflammation that persists in the blood vessels, the brain, the liver, the heart, the kidneys, the gut and the musculo-skeletal system, and is responsible for all the complex pathologies associated with long COVID/PASC. Chronic expression of IL-1, IL-6 and TNFa is critical for the maintenance of the TLR4/RAGE-loop and persistence of long COVID/PASC. 
  • 671
  • 27 Sep 2022
Topic Review
Merkel Cell Polyomavirus and Cancers
Merkel cell polyomavirus (MCPyV), the sole member of Polyomavirus associated with oncogenesis in humans, is the major causative factor of Merkel cell carcinoma (MCC), a rare, neuroendocrine neoplasia of the skin. Many aspects of MCPyV biology and oncogenic mechanisms remain poorly understood.
  • 669
  • 16 Jan 2023
Topic Review
MicroRNAs in Prion Diseases
Prion is an atypical etiological agent composed solely of a misfolded protein—(proteinaceous infectious particle), which affects mammals causing a group of slow, progressive, neurodegenerative, lethal, untreatable disorders known as transmissible spongiform encephalopathies (TSEs).
  • 666
  • 30 Jul 2021
Topic Review
Host Glycobiology/Gut Microbiota in Rotavirus/Norovirus Infection
Rotavirus (RV) and norovirus (NoV) are the leading causes of acute gastroenteritis (AGE) worldwide. Histo-blood group antigens (HBGAs) have a role in NoV and RV infections since their presence on the gut epithelial surfaces is essential for the susceptibility to many NoV and RV genotypes. A second factor that influences enteric viral infections is the gut microbiota of the host. In vitro and animal studies have determined that the gut microbiota limits, but in some cases enhances enteric viral infection. The ways that microbiota can enhance NoV or RV infection include virion stabilization and promotion of virus attachment to host cells, whereas experiments with microbiota-depleted and germ-free animals point to immunoregulation as the mechanism by which the microbiota restrict infection.
  • 666
  • 23 Dec 2021
Topic Review
Major Antimicrobial Peptides Expressed in Lung Airways
The vast surface area of the respiratory system acts as an initial site of contact for microbes and foreign particles. The whole respiratory epithelium is covered with a thin layer of the airway and alveolar secretions. Respiratory secretions contain host defense peptides (HDPs), such as defensins and cathelicidins, which are the best-studied antimicrobial components expressed in the respiratory tract. HDPs have an important role in the human body’s initial line of defense against pathogenic microbes. Epithelial and immunological cells produce HDPs in the surface fluids of the lungs, which act as endogenous antibiotics in the respiratory tract. The production and action of these antimicrobial peptides (AMPs) are critical in the host’s defense against respiratory infections.
  • 663
  • 17 Feb 2023
Topic Review
HIV Latency and Nanomedicine Strategies for Anti-HIV
Antiretrovirals (ARVs) reduce Human Immunodeficiency Virus (HIV) loads to undetectable levels in infected patients. However, HIV can persist throughout the body in cellular reservoirs partly due to the inability of some ARVs to cross anatomical barriers and the capacity of HIV-1 to establish latent infection in resting CD4+ T cells and monocytes/macrophages. A cure for HIV is not likely unless latency is addressed and delivery of ARVs to cellular reservoir sites is improved. Nanomedicine has been used in ARV formulations to improve delivery and efficacy. More specifically, researchers are exploring the benefit of using nanoparticles to improve ARVs and nanomedicine in HIV eradication strategies such as shock and kill, block and lock, and others.
  • 661
  • 13 Jul 2023
Topic Review
Neurotropic Viruses in Mitochondria-Related CNS Disorders
The central nervous system (CNS) is known to be the most energy-demanding system in the human body. Mitochondria are crucial for CNS functionality. Neurotropic viruses such as Herpes, Rabies, West-Nile, and Polioviruses seem to hijack neuronal transport networks, commandeering the proteins that mitochondria typically use to move along neurites.
  • 654
  • 22 Feb 2023
Topic Review
Tissue Specificity of Zika Virus Infection
Zika virus (ZIKV) is an arthropod-borne virus that belongs to the Flavivirus genus and is principally transmitted by Aedes aegypti mosquitoes. ZIKV infection often causes no or only mild symptoms, but it can also trigger severe consequences, including microcephaly in infants and Guillain-Barré syndrome, uveitis, and neurologic manifestations in adults. Since numerous studies have indicated that there are slightly different tissue-specific pathologies in each animal model of ZIKV, the distinct ZIKV tropism of a given animal model must be understood to enable effective vaccine development.
  • 650
  • 22 Sep 2022
Topic Review
Clinical Symptoms and Diagnosis of Tick-Borne Encephalitis
The tick-borne encephalitis virus (TBEV) is the arboviral etiological agent of tick-borne encephalitis (TBE), considered to be one of the most important tick-borne viral diseases in Europe and Asia. 
  • 648
  • 01 Feb 2024
Topic Review
Mechanistic Models in Viral Infection
Mechanistic models are useful to untangle the complex system of virus, cytokines, and immune cells by considering several factors, such as viral entry, replication in target cells, viral spread in the body, immune response, and other complex factors involved in tissue/organ damage and recovery.
  • 638
  • 12 Jan 2023
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