scholarly journals Toll-like Receptors in Viral Encephalitis

Viruses ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2065
Author(s):  
Olivia Luise Gern ◽  
Felix Mulenge ◽  
Andreas Pavlou ◽  
Luca Ghita ◽  
Imke Steffen ◽  
...  

Viral encephalitis is a rare but serious syndrome. In addition to DNA-encoded herpes viruses, such as herpes simplex virus and varicella zoster virus, RNA-encoded viruses from the families of Flaviviridae, Rhabdoviridae and Paramyxoviridae are important neurotropic viruses. Whereas in the periphery, the role of Toll-like receptors (TLR) during immune stimulation is well understood, TLR functions within the CNS are less clear. On one hand, TLRs can affect the physiology of neurons during neuronal progenitor cell differentiation and neurite outgrowth, whereas under conditions of infection, the complex interplay between TLR stimulated neurons, astrocytes and microglia is just on the verge of being understood. In this review, we summarize the current knowledge about which TLRs are expressed by cell subsets of the CNS. Furthermore, we specifically highlight functional implications of TLR stimulation in neurons, astrocytes and microglia. After briefly illuminating some examples of viral evasion strategies from TLR signaling, we report on the current knowledge of primary immunodeficiencies in TLR signaling and their consequences for viral encephalitis. Finally, we provide an outlook with examples of TLR agonist mediated intervention strategies and potentiation of vaccine responses against neurotropic virus infections.

Author(s):  
Peter G. E. Kennedy

Abstract Several viruses have the capacity to cause serious infections of the nervous system in patients who are immunosuppressed. Individuals may be immunosuppressed because of primary inherited immunodeficiency, secondary immunodeficiency due to particular diseases such as malignancy, administration of immunosuppressant drugs or organ or bone marrow transplantation. The viruses capable of such opportunistic infection of the nervous system include herpes simplex virus (HSV), Varicella-Zoster virus (VZV), Cytomegalovirus (CMV), Epstein –Barr virus (EBV), Human Herpes virus type 6 (HHV-6), JC virus (JCV), enterovirus, measles virus and Covid-19. In most cases it seems likely that immunological defence mechanisms in the immunosuppressed are deficient which creates a suitable environment for certain viruses to become opportunistic in the nervous and other systems. Further research is required both to understand these opportunistic mechanisms in more detail and also to determine how many virus infections are modified by specific inborn errors of immunological responses.


Pathogens ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 254 ◽  
Author(s):  
Kathlyn Laval ◽  
Lynn W. Enquist

Pseudorabies virus (PRV) is an alphaherpesvirus related to varicella-zoster virus (VZV) and herpes simplex virus type 1 (HSV1). PRV is the causative agent of Aujeskzy’s disease in swine. PRV infects mucosal epithelium and the peripheral nervous system (PNS) of its host where it can establish a quiescent, latent infection. While the natural host of PRV is the swine, a broad spectrum of mammals, including rodents, cats, dogs, and cattle can be infected. Since the nineteenth century, PRV infection is known to cause a severe acute neuropathy, the so called “mad itch” in non-natural hosts, but surprisingly not in swine. In the past, most scientific efforts have been directed to eradicating PRV from pig farms by the use of effective marker vaccines, but little attention has been given to the processes leading to the mad itch. The main objective of this review is to provide state-of-the-art information on the mechanisms governing PRV-induced neuropathic itch in non-natural hosts. We highlight similarities and key differences in the pathogenesis of PRV infections between non-natural hosts and pigs that might explain their distinctive clinical outcomes. Current knowledge on the neurobiology and possible explanations for the unstoppable itch experienced by PRV-infected animals is also reviewed. We summarize recent findings concerning PRV-induced neuroinflammatory responses in mice and address the relevance of this animal model to study other alphaherpesvirus-induced neuropathies, such as those observed for VZV infection.


1997 ◽  
Vol 10 (4) ◽  
pp. 674-693 ◽  
Author(s):  
E De Clercq

This article describes several approaches to a selective therapy of virus infections: (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU [brivudin]) for the therapy of herpes simplex virus type 1 and varicella-zoster virus infections: (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine (HPMPC [cidofovir]) for the therapy of various DNA virus (i.e., herpesvirus, adenovirus, papillomavirus, polyomavirus, and poxvirus) infections; 9-(2-phosphonylmethoxyethyl)adenine (PMEA [adefovir]) for the therapy of retrovirus, hepadnavirus, and herpesvirus infections; (R)-9-(2-phosphonylmethoxypropyl)adenine (PMPA) for the therapy and prophylaxis of retrovirus and hepadnavirus infections; and nonnucleoside reverse transcriptase inhibitors (NNRTIs), such as tetrahydroimidazo[4,5,1-jk][1,4]-benzodiazepin-2(IH)-one and -thione (TIBO), 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT), alpha-anilinophenylacetamide (alpha-APA), and 2',5'bis-O-(tert-butyldimethylsilyl)-3'-spiro-5"-(4"-amino-1",2"-oxat hiole- 2",2"-dioxide)pyrimidine (TSAO) derivatives, and thiocarboxanilides for the treatment of human immunodeficiency virus type 1 (HIV-1) infections. For the clinical use of NNRTIs, some guidelines have been elaborated, such as starting treatment with combinations of different compounds at sufficiently high concentrations to effect a pronounced and sustained suppression of the virus. Despite the diversity of the compounds described here and the different viruses at which they are targeted, they have a number of characteristics in common. As they interact with specific viral proteins, the compounds achieve a selective inhibition of the replication of the virus, which, in turn, should be able to develop resistance to the compounds. However, as has been established for the NNRTIs, the problem of viral resistance may be overcome if the compounds are used from the start at sufficiently high doses, which could be reduced if different compounds are combined. For HIV infections, drug treatment regimens should be aimed at reducing the viral load to such an extent that the risk for progression to AIDS will be minimized, if not avoided entirely. This may result in a real "cure" of the disease but not necessarily of the virus infection, and in this sense, HIV disease may be reduced to a dormant infection, reminiscent of the latent herpesvirus infections. Should virus replication resume after a certain time, the armamentarium of effective anti-HIV and anti-herpesvirus compounds now available, if applied at the appropriate dosage regimens, should make the virus return to its dormant state before it has any chance to damage the host. It is unlikely that this strategy would eradicate the virus and thus "cure" the viral infection, but it definitely qualifies as a cure of the disease.


2020 ◽  
Vol 8 (6) ◽  
pp. 743-757
Author(s):  
Bhumika Prajapati ◽  
◽  
Kranti Vora ◽  
Aarthi Sundararajan ◽  
Shahin Saiyed ◽  
...  

There is a need for a reliable and cost-effective molecular diagnostic assay for the diagnosis of TORCH [Toxoplasma gondii, Other (Varicella-Zoster virus and Parvovirus B19), Rubella virus, Cytomegalovirus, and Herpes Simplex virus] infections. This would enable early and precise detection of pathogens even in a very low copy number. However, the selection of genomic target, specimen matrix, and different PCR methods can significantly affect the sensitivity and specificity of TORCH molecular detection. This review aimed to provide a comparative analysis of clinical sample types, target nucleotide sequences, and PCR detection approaches for molecular detection of TORCH organisms. This review will aid in the development of a sensitive molecular assay for quick and precise detection of TORCH organisms.


2021 ◽  
Vol 73 (5) ◽  
Author(s):  
Chayada Chaiyabutr ◽  
Nuttagarn Jantanapornchai ◽  
Chalermkwan Apinuntham ◽  
Charussri Leeyaphan ◽  
Sukhum Jiamton

Objective: This research aim to compare (1) the sensitivities and specificities of Tzanck smears and indirect immunofluorescence assays (IFA) for cutaneous HSV and VZV infections in real-life settings; and (2) the detection rates of the tests for various patient types and lesion morphologies.Materials and Methods: This retrospective study reviewed 440 and 172 samples from patients with clinically suspicious cutaneous HSV and VZV infections, respectively. All patients underwent a Tzanck smear and IFA. The gold standard for the study was agreement of pre- and post-diagnostic coding (determined by a dermatologist) for cutaneous HSV and VZV infections.Results: For HSV infections, the respective sensitivity and specificity of Tzanck smears were 32.8% and 96.6%, whereas those for IFA were 60.7% and 100%. As to VZV infections, the sensitivity and specificity of Tzanck smears were 54.3% and 97.8%, respectively, while the corresponding IFA values were 71.7% and 100%. According to disease characteristics and lesion morphologies, the detection ability of cutaneous HSV by IFA was substantially higher than Tzanck smear especially in immunosuppressed condition.  Tzanck smears and IFA demonstrated no statistical difference for early-onset ( 3 days) VZV infections.Conclusion: Tzanck smears and IFA had higher sensitivities for detecting VZV than HSV infections. IFA testing in suspected cutaneous HSV patients with immunosuppressed conditions should be recommended. Despite the overall sensitivity and specificity of IFA being greater than those for Tzanck smears especially in HSV infections, the latter test is a comparable option for early-onset VZV infections.


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