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Viruses Jul 2023Varicella-Zoster virus (VZV) is a pathogenic human alpha herpes virus that causes varicella (chicken pox) as a primary infection and, following a variable period of... (Review)
Review
Varicella-Zoster virus (VZV) is a pathogenic human alpha herpes virus that causes varicella (chicken pox) as a primary infection and, following a variable period of latency in different ganglionic neurons, it reactivates to produce herpes zoster (shingles). The focus of this review is on the wide spectrum of the possible neurological manifestations of VZV reactivation. While the most frequent reactivation syndrome is herpes zoster, this may be followed by the serious and painful post-herpetic neuralgia (PHN) and by many other neurological conditions. Prominent among these conditions is a VZV vasculopathy, but the role of VZV in causing giant cell arteritis (GCA) is currently controversial. VZV reactivation can also cause segmental motor weakness, myelitis, cranial nerve syndromes, Guillain-Barre syndrome, meningoencephalitis, and zoster sine herpete, where a neurological syndrome occurs in the absence of the zoster rash. The field is complicated by the relatively few cases of neurological complications described and by the issue of causation when a neurological condition is not manifest at the same time as the zoster rash.
Topics: Humans; Herpesvirus 3, Human; Herpes Zoster; Chickenpox; Neuralgia, Postherpetic; Alphavirus; Exanthema
PubMed: 37632006
DOI: 10.3390/v15081663 -
Nature Communications Jan 2024Alphaviruses are arboviruses transmitted by mosquitoes and are pathogenic to humans and livestock, causing a substantial public health burden. So far, several receptors...
Alphaviruses are arboviruses transmitted by mosquitoes and are pathogenic to humans and livestock, causing a substantial public health burden. So far, several receptors have been identified for alphavirus entry; however, they cannot explain the broad host range and tissue tropism of certain alphaviruses, such as Getah virus (GETV), indicating the existence of additional receptors. Here we identify the evolutionarily conserved low-density lipoprotein receptor (LDLR) as a new cell entry factor for GETV, Semliki Forest virus (SFV), Ross River virus (RRV) and Bebaru virus (BEBV). Ectopic expression of LDLR facilitates cellular binding and internalization of GETV, which is mediated by the interaction between the E2-E1 spike of GETV and the ligand-binding domain (LBD) of LDLR. Antibodies against LBD block GETV infection in cultured cells. In addition, the GST-LBD fusion protein inhibits GETV infection both in vitro and in vivo. Notably, we identify the key amino acids in LDLR-LBD that played a crucial role in viral entry; specific mutations in the CR4 and CR5 domain of LDLR-LBD reduce viral entry to cells by more than 20-fold. These findings suggest that targeting the LDLR-LBD could be a potential strategy for the development of antivirals against multiple alphaviruses.
Topics: Animals; Humans; Alphavirus; Virus Internalization; Semliki forest virus; Alphavirus Infections; Culicidae
PubMed: 38245515
DOI: 10.1038/s41467-024-44872-5 -
Nature Microbiology Sep 2023Chikungunya virus (CHIKV) has recently emerged to cause millions of human infections worldwide. Infection can induce the formation of long intercellular extensions that...
Chikungunya virus (CHIKV) has recently emerged to cause millions of human infections worldwide. Infection can induce the formation of long intercellular extensions that project from infected cells and form stable non-continuous membrane bridges with neighbouring cells. The mechanistic role of these intercellular extensions in CHIKV infection was unclear. Here we developed a co-culture system and flow cytometry methods to quantitatively evaluate transmission of CHIKV from infected to uninfected cells in the presence of neutralizing antibody. Endocytosis and endosomal acidification were critical for virus cell-to-cell transmission, while the CHIKV receptor MXRA8 was not. By using distinct antibodies to block formation of extensions and by evaluation of transmission in HeLa cells that did not form extensions, we showed that intercellular extensions mediate CHIKV cell-to-cell transmission. In vivo, pre-treatment of mice with a neutralizing antibody blocked infection by direct virus inoculation, while adoptive transfer of infected cells produced antibody-resistant host infection. Together our data suggest a model in which the contact sites of intercellular extensions on target cells shield CHIKV from neutralizing antibodies and promote efficient intercellular virus transmission both in vitro and in vivo.
Topics: Humans; Animals; Mice; Chikungunya virus; HeLa Cells; Chikungunya Fever; Antibodies, Neutralizing; Coculture Techniques
PubMed: 37591996
DOI: 10.1038/s41564-023-01449-0 -
Cancer Cell Feb 2024Although immunotherapy with PD-(L)1 blockade is routine for lung cancer, little is known about acquired resistance. Among 1,201 patients with non-small cell lung cancer...
Although immunotherapy with PD-(L)1 blockade is routine for lung cancer, little is known about acquired resistance. Among 1,201 patients with non-small cell lung cancer (NSCLC) treated with PD-(L)1 blockade, acquired resistance is common, occurring in >60% of initial responders. Acquired resistance shows differential expression of inflammation and interferon (IFN) signaling. Relapsed tumors can be separated by upregulated or stable expression of IFNγ response genes. Upregulation of IFNγ response genes is associated with putative routes of resistance characterized by signatures of persistent IFN signaling, immune dysfunction, and mutations in antigen presentation genes which can be recapitulated in multiple murine models of acquired resistance to PD-(L)1 blockade after in vitro IFNγ treatment. Acquired resistance to PD-(L)1 blockade in NSCLC is associated with an ongoing, but altered IFN response. The persistently inflamed, rather than excluded or deserted, tumor microenvironment of acquired resistance may inform therapeutic strategies to effectively reprogram and reverse acquired resistance.
Topics: Humans; Animals; Mice; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Signal Transduction; Immunotherapy; Antigen Presentation; B7-H1 Antigen; Tumor Microenvironment
PubMed: 38215748
DOI: 10.1016/j.ccell.2023.12.013 -
Revista Da Sociedade Brasileira de... 2023Chikungunya fever (CHIK) is a neglected tropical disease associated with chronic arthritis. CHIK is usually a self-limiting condition; however, extra-articular... (Review)
Review
Chikungunya fever (CHIK) is a neglected tropical disease associated with chronic arthritis. CHIK is usually a self-limiting condition; however, extra-articular manifestations present as atypical illness in a minority of patients. These atypical features may mimic other conditions and potentially distract physicians from the true diagnosis. This review analyzes the evidence of many unusual extra-articular manifestations reported in cases of CHIK. Depending on the affected system, these unusual manifestations include encephalitis, myocarditis, acute interstitial nephritis, cutaneous manifestations, acute anterior uveitis, abdominal pain, and depression. In addition, coinfections and comorbidities may cause atypical illness and obscure the diagnosis. Further studies are required to clarify the pathophysiology and natural history of CHIK, as it remains a burdening condition. Exploring its atypical symptoms may be the missing scientific piece of this puzzle.
Topics: Humans; Chikungunya Fever; Chikungunya virus; Acute Disease; Coinfection; Abdominal Pain
PubMed: 38088664
DOI: 10.1590/0037-8682-0341-2023 -
Viruses Aug 2023Mayaro virus (MAYV), the etiologic agent of Mayaro fever, leads patients to severe myalgia and arthralgia, which can have a major impact on public health in all the... (Review)
Review
Mayaro virus (MAYV), the etiologic agent of Mayaro fever, leads patients to severe myalgia and arthralgia, which can have a major impact on public health in all the countries where the virus circulates. The emergence and dissemination of new viruses have led the scientific community to develop new in vivo models that can help in the fight against new diseases. So far, mice have been the most used animal model in studies with MAYV and have proved to be an adequate model for recapitulating several aspects of the disease observed in humans. Mice are widely used in in vivo research and, therefore, are well known in the scientific community, which has allowed for different strains to be investigated in the study of MAYV. In this review, we summarize the main studies with MAYV using mice as an experimental model and discuss how they can contribute to the advancement of the understanding of its pathogenesis and the development of new drugs and vaccines.
Topics: Humans; Animals; Mice; Alphavirus Infections; Alphavirus; Disease Models, Animal
PubMed: 37766210
DOI: 10.3390/v15091803 -
Journal of Clinical Neurology (Seoul,... Jan 2024Acute infectious encephalitis is a widely studied clinical syndrome. Although identified almost 100 years ago, its immediate and delayed consequences are still neglected... (Review)
Review
Acute infectious encephalitis is a widely studied clinical syndrome. Although identified almost 100 years ago, its immediate and delayed consequences are still neglected despite their high frequency and possible severity. We reviewed the available data on sequelae and persisting symptoms following infectious encephalitis with the aim of characterizing the clinical picture of these patients at months to years after hospitalization. We searched PubMed for case series involving sequelae after infectious encephalitis. We carried out a narrative review of the literature on encephalitis caused by members of the family (herpes simplex virus, varicella zoster virus, and human herpesvirus-6), members of the family (West Nile virus, tick-borne encephalitis virus, and Japanese encephalitis virus), alphaviruses, and Nipah virus. We retrieved 41 studies that yielded original data involving 3,072 adult patients evaluated after infectious encephalitis. At least one of the five domains of cognitive outcome, psychiatric disorders, neurological deficits, global functioning, and quality of life was investigated in the reviewed studies. Various tests were used in the 41 studies and the investigation took place at different times after hospital discharge. The results showed that most patients are discharged with impairments, with frequent deficits in cognitive function such as memory loss or attention disorders. Sequelae tend to improve within several years following flavivirus or Nipah virus infection, but long-term data are scarce for other pathogens. Further research is needed to better understand the extent of sequelae after infectious encephalitis, and to propose a standardized assessment method and assess the rehabilitation efficacy in these patients.
PubMed: 38179629
DOI: 10.3988/jcn.2023.0240