Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 10 de 10
Filter
1.
Viruses ; 13(7)2021 07 15.
Article in English | MEDLINE | ID: covidwho-1448933

ABSTRACT

Virus-induced infections of the central nervous system (CNS) are among the most serious problems in public health and can be associated with high rates of morbidity and mortality, mainly in low- and middle-income countries, where these manifestations have been neglected. Typically, herpes simplex virus 1 and 2, varicella-zoster, and enterovirus are responsible for a high number of cases in immunocompetent hosts, whereas other herpesviruses (for example, cytomegalovirus) are the most common in immunocompromised individuals. Arboviruses have also been associated with outbreaks with a high burden of neurological disorders, such as the Zika virus epidemic in Brazil. There is a current lack of understanding in Brazil about the most common viruses involved in CNS infections. In this review, we briefly summarize the most recent studies and findings associated with the CNS, in addition to epidemiological data that provide extensive information on the circulation and diversity of the most common neuro-invasive viruses in Brazil. We also highlight important aspects of the prion-associated diseases. This review provides readers with better knowledge of virus-associated CNS infections. A deeper understanding of these infections will support the improvement of the current surveillance strategies to allow the timely monitoring of the emergence/re-emergence of neurotropic viruses.


Subject(s)
Central Nervous System Diseases/virology , Central Nervous System Infections/epidemiology , Prion Diseases/epidemiology , Alphavirus/pathogenicity , Brazil/epidemiology , Central Nervous System/virology , Central Nervous System Diseases/metabolism , Central Nervous System Diseases/physiopathology , Central Nervous System Infections/virology , Central Nervous System Viral Diseases/physiopathology , Central Nervous System Viral Diseases/virology , Enterovirus/pathogenicity , Flavivirus/pathogenicity , Herpesviridae/pathogenicity , Humans , Nervous System Diseases/epidemiology , Nervous System Diseases/virology , Prion Diseases/physiopathology , Prions/metabolism , Prions/pathogenicity , Simplexvirus/pathogenicity , Virus Diseases/virology , Viruses/pathogenicity , Zika Virus/pathogenicity
2.
Viruses ; 13(10)2021 10 02.
Article in English | MEDLINE | ID: covidwho-1441885

ABSTRACT

Viral proteases are indispensable for successful virion maturation, thus making them a prominent drug target. Their enzyme activity is tightly spatiotemporally regulated by expression in the precursor form with little or no activity, followed by activation via autoprocessing. These cleavage events are frequently triggered upon transportation to a specific compartment inside the host cell. Typically, precursor oligomerization or the presence of a co-factor is needed for activation. A detailed understanding of these mechanisms will allow ligands with non-canonical mechanisms of action to be designed, which would specifically modulate the initial irreversible steps of viral protease autoactivation. Binding sites exclusive to the precursor, including binding sites beyond the protease domain, can be exploited. Both inhibition and up-regulation of the proteolytic activity of viral proteases can be detrimental for the virus. All these possibilities are discussed using examples of medically relevant viruses including herpesviruses, adenoviruses, retroviruses, picornaviruses, caliciviruses, togaviruses, flaviviruses, and coronaviruses.


Subject(s)
Antiviral Agents/pharmacology , Viral Protease Inhibitors/pharmacology , Viral Proteases/metabolism , Virus Diseases/drug therapy , Adenoviruses, Human/drug effects , Adenoviruses, Human/metabolism , Flavivirus/drug effects , Flavivirus/metabolism , HIV-1/drug effects , Herpesviridae/drug effects , Herpesviridae/metabolism , Humans , SARS-CoV-2/drug effects , SARS-CoV-2/metabolism , Viral Proteases/biosynthesis
3.
Int J Mol Sci ; 22(10)2021 May 17.
Article in English | MEDLINE | ID: covidwho-1383880

ABSTRACT

Numerous viruses hijack cellular protein trafficking pathways to mediate cell entry or to rearrange membrane structures thereby promoting viral replication and antagonizing the immune response. Adaptor protein complexes (AP), which mediate protein sorting in endocytic and secretory transport pathways, are one of the conserved viral targets with many viruses possessing AP-interacting motifs. We present here different mechanisms of viral interference with AP complexes and the functional consequences that allow for efficient viral propagation and evasion of host immune defense. The ubiquity of this phenomenon is evidenced by the fact that there are representatives for AP interference in all major viral families, covered in this review. The best described examples are interactions of human immunodeficiency virus and human herpesviruses with AP complexes. Several other viruses, like Ebola, Nipah, and SARS-CoV-2, are pointed out as high priority disease-causative agents supporting the need for deeper understanding of virus-AP interplay which can be exploited in the design of novel antiviral therapies.


Subject(s)
Adaptor Proteins, Vesicular Transport/metabolism , HIV-1/metabolism , Herpesviridae/metabolism , SARS-CoV-2/metabolism , Ebolavirus/metabolism , Endocytosis , Humans , Nipah Virus/metabolism , Protein Transport , Virus Release , Virus Replication
4.
Infect Dis Now ; 51(8): 676-679, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1330850

ABSTRACT

OBJECTIVE: We assessed herpesvirus reactivation in severe SARS-CoV-2 infection. METHODS: Retrospective study including consecutive patients admitted to an onco-hematology intensive care unit (ICU) for severe COVID-19. Replication of EBV, CMV, and HSV was evaluated. Competing risk analyses were used to assess the cumulative risk of viral reactivation, and time-dependent Cox and Fine and Gray models to assess risk factors for viral reactivation. RESULTS: Among 100 patients, 38 were immunocompromised. Sixty-three patients presented viral reactivation (12% for HSV, 58% EBV and 19% CMV). Symptomatic patients received treatment. Overall cumulative incidence of viral reactivation was 56.1% [55.9-56.4] at 10 days. After adjustment, a preexisting hematological malignancy (sHR [95%CI]=0.31 [0.11-0.85]) and solid organ transplantation (sHR [95% CI]=2.09 [1.13-3.87]) remained independently associated with viral reactivation. Viral reactivation (P=0.34) was not associated with mortality. CONCLUSIONS: Incidence of herpesvirus reactivation in patients admitted to the ICU for severe COVID-19 was high, but rarely required antiviral treatment.


Subject(s)
COVID-19 , Herpesviridae , Critical Illness , Humans , Retrospective Studies , SARS-CoV-2
6.
Biomolecules ; 10(8)2020 08 01.
Article in English | MEDLINE | ID: covidwho-1023242

ABSTRACT

Posttranslational modifications of cellular proteins by covalent conjugation of ubiquitin and ubiquitin-like polypeptides regulate numerous cellular processes that are captured by viruses to promote infection, replication, and spreading. The importance of these protein modifications for the viral life cycle is underscored by the discovery that many viruses encode deconjugases that reverse their functions. The structural and functional characterization of these viral enzymes and the identification of their viral and cellular substrates is providing valuable insights into the biology of viral infections and the host's antiviral defense. Given the growing body of evidence demonstrating their key contribution to pathogenesis, the viral deconjugases are now recognized as attractive targets for the design of novel antiviral therapeutics.


Subject(s)
Antiviral Agents/pharmacology , Enzymes/metabolism , Host-Pathogen Interactions/physiology , Ubiquitin/metabolism , Viral Proteins/metabolism , Virus Diseases/metabolism , Adenoviridae/enzymology , Coronavirus/enzymology , Enzymes/chemistry , Herpesviridae/enzymology , Humans , Protein Processing, Post-Translational , Viral Proteins/chemistry , Virus Diseases/drug therapy
7.
Front Immunol ; 11: 594963, 2020.
Article in English | MEDLINE | ID: covidwho-1094164

ABSTRACT

When viruses infect cells, they almost invariably cause metabolic changes in the infected cell as well as in several host cell types that react to the infection. Such metabolic changes provide potential targets for therapeutic approaches that could reduce the impact of infection. Several examples are discussed in this review, which include effects on energy metabolism, glutaminolysis and fatty acid metabolism. The response of the immune system also involves metabolic changes and manipulating these may change the outcome of infection. This could include changing the status of herpesviruses infections from productive to latency. The consequences of viral infections which include coronavirus disease 2019 (COVID-19), may also differ in patients with metabolic problems, such as diabetes mellitus (DM), obesity, and endocrine diseases. Nutrition status may also affect the pattern of events following viral infection and examples that impact on the pattern of human and experimental animal viral diseases and the mechanisms involved are discussed. Finally, we discuss the so far few published reports that have manipulated metabolic events in-vivo to change the outcome of virus infection. The topic is expected to expand in relevance as an approach used alone or in combination with other therapies to shape the nature of virus induced diseases.


Subject(s)
COVID-19/metabolism , Herpesviridae Infections/metabolism , Herpesviridae/physiology , Obesity/metabolism , SARS-CoV-2/physiology , Animals , COVID-19/complications , Energy Metabolism , Herpesviridae Infections/complications , Humans , Immunity , Lipid Metabolism , Nutritional Physiological Phenomena , Obesity/complications , Pandemics , Virus Latency
8.
Arch Virol ; 166(3): 733-753, 2021 Mar.
Article in English | MEDLINE | ID: covidwho-1064515

ABSTRACT

The chronic dysfunction of neuronal cells, both central and peripheral, a characteristic of neurological disorders, may be caused by irreversible damage and cell death. In 2016, more than 276 million cases of neurological disorders were reported worldwide. Moreover, neurological disorders are the second leading cause of death. Generally, the etiology of neurological diseases is not fully understood. Recent studies have related the onset of neurological disorders to viral infections, which may cause neurological symptoms or lead to immune responses that trigger these pathological signs. Currently, this relationship is mostly based on epidemiological data on infections and seroprevalence of patients who present with neurological disorders. The number of studies aiming to elucidate the mechanism of action by which viral infections may directly or indirectly contribute to the development of neurological disorders has been increasing over the years but these studies are still scarce. Comprehending the pathogenesis of these diseases and exploring novel theories may favor the development of new strategies for diagnosis and therapy in the future. Therefore, the objective of the present study was to review the main pieces of evidence for the relationship between viral infection and neurological disorders such as Alzheimer's disease, Parkinson's disease, Guillain-Barré syndrome, multiple sclerosis, and epilepsy. Viruses belonging to the families Herpesviridae, Orthomyxoviridae, Flaviviridae, and Retroviridae have been reported to be involved in one or more of these conditions. Also, neurological symptoms and the future impact of infection with SARS-CoV-2, a member of the family Coronaviridae that is responsible for the COVID-19 pandemic that started in late 2019, are reported and discussed.


Subject(s)
COVID-19/pathology , Nervous System Diseases/virology , Viral Tropism/physiology , Alzheimer Disease/virology , COVID-19/virology , Epilepsy/virology , Flaviviridae/metabolism , Guillain-Barre Syndrome/virology , Herpesviridae/metabolism , Humans , Multiple Sclerosis/virology , Nervous System Diseases/pathology , Orthomyxoviridae/metabolism , Parkinson Disease/virology , Retroviridae/metabolism , SARS-CoV-2/metabolism
10.
Viruses ; 12(4)2020 04 23.
Article in English | MEDLINE | ID: covidwho-108836

ABSTRACT

The whole world is currently facing an unseen enemy, called coronavirus disease 2019 (COVID-19), which is causing a global pandemic. This disease is caused by a novel single-stranded enveloped RNA virus, known as the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). Although huge efforts are being made to produce effective therapies to combat this disease, it continues to be one of the greatest challenges in medicine. There is no doubt that herpesviruses are one of the most important viruses that infect humans and animals, and infections induced by these pathogens have developed into a great threat to public health. According to the currently available evidence, the correlation between herpesviruses and coronaviruses is limited to the induced complications following the infections. For instance, the inflammation that is induced at the sites of infection could tie these viruses to each other in a relationship. Another example, bovine herpesvirus 1, which is an important pathogen of cattle, can cause a severe respiratory infection; the same way in which SARS-CoV-2 affects humans. Considering the current circumstances related to the COVID-19 crisis, this editorial paper, which belongs to the Special Issue "Recent Advances in Herpesviruses Research: What's in the Pipeline?" aims to draw attention to some natural anti-herpesvirus alkaloid compounds, which have recently been proven to have excellent inhibitory efficacy against SARS-CoV-2 replication. Thus, this special focus is an attempt to hunt down various treatment options to combat COVID-19 based on repurposing drugs that are known to have multiple antiviral properties, including against herpesvirus.


Subject(s)
Alkaloids/pharmacology , Coronavirus Infections/drug therapy , Herpesviridae/drug effects , Plant Extracts/pharmacology , Pneumonia, Viral/drug therapy , Animals , Antiviral Agents/pharmacology , Betacoronavirus/drug effects , COVID-19 , Herpesviridae Infections/drug therapy , Humans , Pandemics , Plant Extracts/therapeutic use , SARS-CoV-2
SELECTION OF CITATIONS
SEARCH DETAIL
...