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Microbes and Infection 2023Human Angiotensin-Converting Enzyme 2 (hACE2) is the major receptor enabling host cell invasion by SARS-CoV-2 via interaction with Spike. The murine ACE2 does not...
Human Angiotensin-Converting Enzyme 2 (hACE2) is the major receptor enabling host cell invasion by SARS-CoV-2 via interaction with Spike. The murine ACE2 does not interact efficiently with SARS-CoV-2 Spike and therefore the laboratory mouse strains are not permissive to SARS-CoV-2 replication. Here, we generated new hACE2 transgenic mice, which harbor the hACE2 gene under the human keratin 18 promoter, in "HHD-DR1" background. HHD-DR1 mice are fully devoid of murine Major Histocompatibility Complex (MHC) molecules of class-I and -II and express only MHC molecules from Human Leukocyte Antigen (HLA) HLA 02.01, DRA01.01, DRB1.01.01 alleles, widely expressed in human populations. We selected three transgenic strains, with various hACE2 mRNA expression levels and distinctive profiles of lung and/or brain permissiveness to SARS-CoV-2 replication. These new hACE2 transgenic strains display high permissiveness to the replication of SARS-CoV-2 Omicron sub-variants, while the previously available B6.K18-ACE2 mice have been reported to be poorly susceptible to infection with Omicron. As a first application, one of these MHC- and ACE2-humanized strains was successfully used to show the efficacy of a lentiviral-based COVID-19 vaccine.
Topics: Animals; Mice; Humans; Angiotensin-Converting Enzyme 2; SARS-CoV-2; COVID-19 Vaccines; Permissiveness; COVID-19; Major Histocompatibility Complex; Mice, Transgenic
PubMed: 37080384
DOI: 10.1016/j.micinf.2023.105142 -
Virology May 2016Polydnaviruses in the genus Bracovirus (BV) are associated with parasitoid wasps in the family Braconidae. BV-carrying wasps rely on their associated viruses to...
Polydnaviruses in the genus Bracovirus (BV) are associated with parasitoid wasps in the family Braconidae. BV-carrying wasps rely on their associated viruses to parasitize permissive hosts but also occasionally oviposit into host species that are non-permissive. Here, we studied Microplitis demolitor and M. demolitor bracovirus (MdBV) in Chrysodeixis includens, a permissive host, and Trichoplusia ni, which is usually non-permissive. M. demolitor laid eggs and injected MdBV into both hosts but almost no wasp offspring developed in T. ni. MdBV DNA similarly persisted in both host species, but deep sequencing data showed that transcript abundance for most viral genes was higher in C. includens than T. ni. Overall, our results identify lower expression of MdBV genes as an important factor in the non-permissiveness of T. ni. However, certain genes with functions in immunosuppression were sufficiently expressed to have similar effect in T. ni and C. includens.
Topics: Animals; Cell Line; Gene Expression Profiling; Gene Expression Regulation, Viral; Genes, Viral; High-Throughput Nucleotide Sequencing; Host Specificity; Larva; Moths; Polydnaviridae; Viral Proteins; Wasps
PubMed: 27011224
DOI: 10.1016/j.virol.2016.02.023 -
MBio Dec 2022Human immunodeficiency virus type 1 (HIV-1) can integrate viral DNA into host cell chromosomes to establish a long-term stable latent reservoir, which is a major...
Human immunodeficiency virus type 1 (HIV-1) can integrate viral DNA into host cell chromosomes to establish a long-term stable latent reservoir, which is a major obstacle to cure HIV-1 infection. The characteristics of the HIV-1 latent reservoir have not been fully understood. Here, we identified 126 upregulated plasma membrane proteins in HIV-1 latently infected cells by a label-free liquid chromatography-tandem mass spectrometry analysis. The higher levels of CD98 expression in multiple HIV-1 latently infected cell lines and primary CD4 T cells compared to uninfected cells were further confirmed by quantitative reverse transcription PCR (RT-qPCR) and flow cytometry analyses. In addition, CD98 CD4 T cells displayed hyper-permissiveness to HIV-1 infection and possessed distinct immune phenotypic profiles associated with Th17 and peripheral follicular T helper (pTFH) characteristics. Notably, the CD98 resting memory CD4 T cells harbored significantly higher cell-associated viral RNA and intact provirus than CD98 counterparts in HIV-1-infected individuals receiving combined antiretroviral therapy. Furthermore, CD98 CD4 T cells exhibited a robust proliferative capacity and significantly contributed to the clonal expansion of the HIV-1 latent reservoir. Our study demonstrates that CD98 can be used as a novel biomarker of HIV-1 latently infected cells to indicate the effect of various strategies to reduce the viral reservoir. Identification of cellular biomarkers is the crucial challenge to eradicate the HIV-1 latent reservoir. In our study, we identified CD98 as a novel plasma membrane biomarker for HIV-1 permissiveness and latent infection. Importantly, CD98 CD4 T cells exhibited a hyper-permissiveness to HIV-1 infection and significantly contributed to the clonal expansion of the HIV-1 latent reservoir. CD98 could be targeted to develop therapeutic strategies to reduce the HIV-1 latent reservoir in further research.
Topics: Humans; Biomarkers; CD4-Positive T-Lymphocytes; HIV Infections; HIV-1; Latent Infection; Permissiveness; Virus Latency; Virus Replication; Fusion Regulatory Protein-1
PubMed: 36214569
DOI: 10.1128/mbio.02496-22 -
Psicothema 2013Parents play an important role in determining the risk of children's drug use. The aim of this study was to analyse how certain family-related variables (permissiveness...
BACKGROUND
Parents play an important role in determining the risk of children's drug use. The aim of this study was to analyse how certain family-related variables (permissiveness toward drug use, and parental control and affect) were linked to the use of alcohol, tobacco and cannabis, based on young people's self-report of such variables.
METHOD
The sample was composed of 1,428 school children (51.8% males) aged between 11 and 19 from Mallorca (Spain).
RESULTS
We found that the young people who perceived their parents as permissive and those who perceived less maternal control and higher levels of both paternal and maternal affect were more likely to use alcohol, tobacco and cannabis. Sex differences were found within this pattern. Variables of maternal affect and control were not influential among males, whereas the general pattern was maintained among females.
CONCLUSIONS
This study highlights the importance of perceived permissiveness and the need of considering parent's and children's gender when providing control and affect, as fathers will influence male children whereas mothers will influence female children.
Topics: Adolescent; Affect; Child; Child Rearing; Cross-Sectional Studies; Female; Humans; Male; Parent-Child Relations; Permissiveness; Substance-Related Disorders
PubMed: 23910741
DOI: 10.7334/psicothema2012.294 -
Journal of Medical Entomology Jan 2023A cell line was established from Culex tarsalis Coquillett embryonated eggs and designated as CxTr. The cell line is heterogeneous, composed predominantly of small,...
A cell line was established from Culex tarsalis Coquillett embryonated eggs and designated as CxTr. The cell line is heterogeneous, composed predominantly of small, round cells, and spindle-shaped cells with a doubling time of approximately 52-60 h. The identity of the cell line was verified as Cx. tarsalis by sequencing of cytochrome oxidase I and the cells were found to be free of contaminating cells, bacteria, fungi, and mycoplasma. The permissiveness of CxTr cells to arbovirus infection was investigated with vaccine and wildtype arboviruses from four viral families: Flaviviridae (Japanese encephalitis virus), Phenuiviridae (Rift Valley fever phlebovirus), Rhabdoviridae (vesicular stomatitis virus), and Togaviridae (Mayaro virus). All viruses were able to infect and replicate within CxTr cells.
Topics: Animals; Culicidae; Culex; Permissiveness; Arbovirus Infections; Cell Line
PubMed: 36260075
DOI: 10.1093/jme/tjac155 -
Current Opinion in Immunology Oct 2023Macrophages function as tissue-immune sentinels and mediate key antimicrobial responses against bacterial pathogens. Yet, they can also act as a cellular niche for... (Review)
Review
Macrophages function as tissue-immune sentinels and mediate key antimicrobial responses against bacterial pathogens. Yet, they can also act as a cellular niche for intracellular bacteria, such as Salmonella enterica, to persist in infected tissues. Macrophages exhibit heterogeneous activation or polarization, states that are linked to differential antibacterial responses and bacteria permissiveness. Remarkably, recent studies demonstrate that Salmonella and other intracellular bacteria inject virulence effectors into the cellular cytoplasm to skew the macrophage polarization state and reprogram these immune cells into a permissive niche. Here, we review mechanisms of macrophage reprogramming by Salmonella and highlight manipulation of macrophage polarization as a shared bacterial pathogenesis strategy. In addition, we discuss how the interplay of bacterial effector mechanisms, microenvironmental signals, and ontogeny may shape macrophage cell states and functions. Finally, we propose ideas of how further research will advance our understanding of macrophage functional diversity and immunobiology.
Topics: Humans; Macrophages; Bacteria; Virulence
PubMed: 37437470
DOI: 10.1016/j.coi.2023.102367 -
The European Respiratory Journal Dec 2022SARS-CoV-2 has caused devastating effects with over 550 million infections by July 2022 and approximately 6.4 million deaths [1]. Societal and economic impacts will...
SARS-CoV-2 has caused devastating effects with over 550 million infections by July 2022 and approximately 6.4 million deaths [1]. Societal and economic impacts will reverberate for years, with continuous evolution of SARS-CoV-2 as it persistently spreads through the human population as exemplified by reduced activity of vaccines and monoclonals against Omicron BA.4 or BA.5 subvariants [2]. A greater understanding of pathogenesis and more tailored therapeutic approaches are therefore essential.
Topics: Humans; SARS-CoV-2; COVID-19; Angiotensin-Converting Enzyme 2; Permissiveness; Lung; Inflammation; Macrophages
PubMed: 36028257
DOI: 10.1183/13993003.01521-2022 -
Journal of Virology Jun 2014Oncolytic viruses (OVs) are attractive avenues of cancer therapy due to the absence of toxic side effects often seen with current treatment modalities. Bovine...
UNLABELLED
Oncolytic viruses (OVs) are attractive avenues of cancer therapy due to the absence of toxic side effects often seen with current treatment modalities. Bovine herpesvirus 1 (BHV-1) is a species-specific virus that does not induce cytotoxicity in normal primary human cells but can infect and kill various human immortalized and transformed cell lines. To gain a better understanding of the oncolytic breadth of BHV-1, the NCI panel of established human tumor cell lines was screened for sensitivity to the virus. Overall, 72% of the panel is permissive to BHV-1 infection, with corresponding decreases in cellular viability. This sensitivity is in comparison to a sensitivity of only 32% for a herpes simplex virus 1 (HSV-1)-based oncolytic vector. Strikingly, while 35% of the panel supports minimal or no BHV-1 replication, significant decreases in cellular viability still occur. These data suggest that BHV-1 is an OV with tropism for multiple tumor types and is able to induce cytotoxicity independent of significant virus replication. In contrast to other species-specific OVs, cellular sensitivity to BHV-1 does not correlate with type I interferon (IFN) signaling; however, mutations in KRAS were found to correlate with high levels of virus replication. The knockdown or overexpression of KRAS in human tumor cell lines yields modest changes in viral titers; however, overexpression of KRAS in normal primary cells elicits permissivity to BHV-1 infection. Together, these data suggest that BHV-1 is a broad-spectrum OV with a distinct mechanism of tumor targeting.
IMPORTANCE
Cancer remains a significant health issue, and novel treatments are required, particularly for tumors that are refractory to conventional therapies. Oncolytic viruses are a novel platform given their ability to specifically target tumor cells while leaving healthy cells intact. For this strategy to be successful, a fundamental understanding of virus-host interactions is required. We previously identified bovine herpesvirus 1 as a novel oncolytic virus with many unique and clinically relevant features. Here, we show that BHV-1 can target a wide range of human cancer types, most potently lung cancer. In addition, we show that enhanced KRAS activity, a hallmark of many cancers, is one of the factors that increases BHV-1 oncolytic capacity. These findings hold potential for future treatments, particularly in the context of lung cancer, where KRAS mutations are a negative predictor of treatment efficacy.
Topics: Animals; Cell Line, Tumor; Humans; Neoplasms; Oncolytic Virotherapy; Oncolytic Viruses; Proto-Oncogene Proteins; Proto-Oncogene Proteins p21(ras); Virus Replication; ras Proteins
PubMed: 24696490
DOI: 10.1128/JVI.00849-14 -
Voprosy Virusologii Mar 2021Bats are an epidemiologically important natural reservoir of viruses of various taxonomic groups, including causative agents of especially dangerous infections of humans...
INTRODUCTION
Bats are an epidemiologically important natural reservoir of viruses of various taxonomic groups, including causative agents of especially dangerous infections of humans and animals. Considering the relevance of arbovirus infections, it seems advisable to study the spectrum of the sensitivity of cells derived from bats inhabiting and migrating on the territory of the Russian Federation to causative agents of vector-borne diseases of animals.The study aimed to obtain a diploid strain of cells from renal tissue of bats Pipistrellus nathusii and to investigate its biological characteristics, as well as to assess its permissiveness for bluetongue (BTV); Rift Valley fever (RVFV); lumpy skin disease (LSDV); rabbit myxoma (Myxomatosis cuniculi); rabbit, or Shope fibroma (RFV); African horse sickness (AHSV) and African swine fever (ASFV) viruses.
MATERIAL AND METHODS
There were 2 clinically healthy male individuals of P. nathusii who taken as donors of organs. To obtain diploid kidney cell culture strain and to study its properties, the level of the 6th passage was investigated by conventional cytological, virological, and molecular methods. The permissiveness of the obtained cell culture for BTV, RVFV, LSDV, Myxomatosis cuniculi, RFV, AHSV and ASFV was determined.
RESULTS
The formation of a confluent monolayer was observed after 72 hours, while the proliferation index was 2.7-3.3. The cell monolayer had been maintained without changing the medium for 45 days (observation period). The stability of the karyotype had been demonstrated in continuous subculturing at the 36th passage. The cell culture named «Diploid cell line Pipistrellus nathusii kidney», and its permissiveness to BTV, RVFV, LSDV and Myxomatosis cuniculi had been demonstrated.
DISCUSSION
The sensitivity of the strain to BTV and RVFV is consistent with the data on the identification of reovirus and RVFV in Egyptian fruit bats (Rousettus aegyptiacus), and its permissiveness for LSDV and rabbits myxoma virus is consistent with the results of detection of poxviruses in big brown bat (Eptesicus fuscus).
CONCLUSION
A diploid kidney cell strain derived from P. nathusii was obtained and certified. Its permissiveness to BTV, RVFV, LSDV and rabbits myxoma viruses makes it possible to use this strain for isolation and studies of these viruses. Reproduction of the viruses in diploid kidney cells strain derived from P. nathusii living and migrating in the European part of the Russian Federation indicates their potential role in the epidemiology of significant infections, especially transmissible ones.
Topics: African Swine Fever; Animals; Cattle; Chiroptera; Diploidy; Kidney; Male; Permissiveness; Rabbits; Swine; Viruses
PubMed: 33683063
DOI: 10.36233/0507-4088-12 -
Viruses Nov 2022Mast cells (MCs) are classically associated with allergic asthma but their role in antiviral immunity is unclear. Human rhinoviruses (HRVs) are a major cause of asthma...
Mast cells (MCs) are classically associated with allergic asthma but their role in antiviral immunity is unclear. Human rhinoviruses (HRVs) are a major cause of asthma exacerbations and can infect and replicate within MCs. The primary site of HRV infection is the airway epithelium and MCs localise to this site with increasing asthma severity. The asthma susceptibility gene, IL-33, encodes an epithelial-derived cytokine released following HRV infection but its impact on MC antiviral responses has yet to be determined. In this study we investigated the global response of LAD2 MCs to IL-33 stimulation using RNA sequencing and identified genes involved in antiviral immunity. In spite of this, IL-33 treatment increased permissiveness of MCs to HRV16 infection which, from the RNA-Seq data, we attributed to upregulation of ICAM1. Flow cytometric analysis confirmed an IL-33-dependent increase in ICAM1 surface expression as well as LDLR, the receptors used by major and minor group HRVs for cellular entry. Neutralisation of ICAM1 reduced the IL-33-dependent enhancement in HRV16 replication and release in both LAD2 MCs and cord blood derived MCs. These findings demonstrate that although IL-33 induces an antiviral signature in MCs, it also upregulates the receptors for HRV entry to enhance infection. This highlights the potential for a gene-environment interaction involving IL33 and HRV in MCs to contribute to virus-induced asthma exacerbations.
Topics: Humans; Rhinovirus; Interleukin-33; Mast Cells; Antiviral Agents; Permissiveness; Virus Replication; Asthma; Epithelial Cells; Picornaviridae Infections
PubMed: 36366528
DOI: 10.3390/v14112430