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Scientific Reports Jan 2021The relationship between viral infection and obesity has been known for several decades but epidemiological data is limited to only a few viral pathogens. The...
The relationship between viral infection and obesity has been known for several decades but epidemiological data is limited to only a few viral pathogens. The association between obesity and a wide range of viruses was assessed using VirScan, a pan-viral serological profiling tool. Serum specimens from 457 Qatari adults (lean = 184; obese = 273) and 231 Qatari children (lean = 111; obese = 120) were analyzed by VirScan. Associations with obesity were determined by odds ratio (OR) and Fisher's test (p values), and by multivariate regression analysis to adjust for age and gender. Although there was no association of viral infections with obesity in the pediatric population, a nominal association of obesity with seropositivity to members of the Herpesviridae family is observed for the adult population (OR = 1.5-3.3; p < 0.05). After adjusting p values for multiple comparisons (Bonferroni correction) the odds of being obese is significantly higher in herpes simplex virus 1 (HSV-1) seropositive Qatari adults (OR = 3.3; 95% CI 2.15-4.99; p = 2.787E - 08). By VirScan, the sero-prevalence of HSV1 is 81.3% and 57.1% among Qatari obese and lean adult populations, respectively. Higher prevalence of antibodies against several peptide epitopes of HSV-1/2 is positively associated with obesity (OR = 2.35-3.82; p ≤ 3.981E - 05). By multivariate regression analysis, HSV-1 was independently associated with obesity irrespective of age and gender. Our results suggest that obesity among Qataris may be associated with a higher prevalence of herpesvirus infections, in particular HSV-1. Furthermore, the high prevalence of antibodies against peptide antigens specific to HSV-1 and -2 in the obese population suggests that these viral peptides may play a role in adipogenesis. Further studies with these candidate peptides in cell culture or animal models may confirm their adipogenic roles.
Topics: Adult; Endocrine System; Female; Herpesviridae; Humans; Male; Metabolic Diseases; Middle Aged; Obesity; Virology; Virome
PubMed: 33510449
DOI: 10.1038/s41598-021-82213-4 -
The Lancet. Oncology Jun 2021Non-AIDS-defining cancers are a growing source of morbidity for people with HIV globally. Although people living with HIV have a disproportionately increased risk of... (Review)
Review
Non-AIDS-defining cancers are a growing source of morbidity for people with HIV globally. Although people living with HIV have a disproportionately increased risk of developing virally mediated cancers, cancer burden for common non-AIDS-defining cancers that are not virally associated and are linked to ageing, such as prostate cancer, is becoming higher than for virally mediated cancers. Ageing, behavioural, and HIV-specific factors drive the incidence and affect the outcomes of non-AIDS-defining cancers, presenting different challenges for addressing global morbidity and mortality from non-AIDS-defining cancer. Although large population-based studies have shown that people living with HIV with non-AIDS-defining cancers have poorer cancer outcomes than do people without HIV, current guidelines emphasise that people living with HIV with non-AIDS-defining cancers should receive standard, guideline-based treatment, and infectious disease and oncology providers should work closely to address potential drug interactions between antiretroviral therapy and antineoplastic treatment. Most trials target preventive measures focusing on non-AIDS-defining cancers. However, treatment trials for the optimal management of people living with HIV and non-AIDS-defining cancer, including interventions such as immunotherapies, are needed to improve non-AIDS-defining cancer outcomes.
Topics: Acquired Immunodeficiency Syndrome; Antiretroviral Therapy, Highly Active; HIV; HIV Infections; Humans; Immunotherapy; Neoplasms; Risk Factors; Sarcoma, Kaposi; Treatment Outcome
PubMed: 34087151
DOI: 10.1016/S1470-2045(21)00137-6 -
Vaccine Apr 2022Vaccine platforms have been critical for accelerating the timeline of COVID-19 vaccine development. Faster vaccine timelines demand further development of these...
Vaccine platforms have been critical for accelerating the timeline of COVID-19 vaccine development. Faster vaccine timelines demand further development of these technologies. Currently investigated platform approaches include virally vectored and RNA-based vaccines, as well as DNA vaccines and recombinant protein expression system platforms, each featuring different advantages and challenges. Viral vector-based and DNA vaccines in particular have received a large share of research funding to date. Platform vaccine technologies may feature dual-use potential through informing or enabling pathogen engineering, which may raise the risk for the occurrence of deliberate, anthropogenic biological events. Research on virally vectored vaccines exhibits relatively high dual-use potential for two reasons. First, development of virally vectored vaccines may generate insights of particular dual-use concern such as techniques for circumventing pre-existing anti-vector immunity. Second, while the amount of work on viral vectors for gene therapy exceeds that for vaccine research, work on virally vectored vaccines may increase the number of individuals capable of engineering viruses of particular concern, such as ones closely related to smallpox. Other platform vaccine approaches, such as RNA vaccines, feature relatively little dual-use potential. The biosecurity risk associated with platform advancement may be minimised by focusing preferentially on circumventing anti-vector immunity with non-genetic rather than genetic modifications, using vectors that are not based on viruses pathogenic to humans, or preferential investment into promising RNA-based vaccine approaches. To reduce the risk of anthropogenic pandemics, structures for the governance of biotechnology and life science research with dual-use potential need to be reworked. Scientists outside of the pathogen research community, for instance those who work on viral vectors or oncolytic viruses, need to become more aware of the dual-use risks associated with their research. Both public and private research-funding bodies need to prioritise the evaluation and reduction of biosecurity risks.
Topics: Biosecurity; COVID-19; COVID-19 Vaccines; Genetic Vectors; Humans; RNA; Vaccines, DNA; Viral Vaccines; Viruses
PubMed: 33640142
DOI: 10.1016/j.vaccine.2021.02.023 -
Pathogens (Basel, Switzerland) Feb 2020Zika virus (ZIKV) is a mosquito-borne virus associated with neurological disorders such as Guillain-Barré syndrome and microcephaly. In humans, ZIKV is able to... (Review)
Review
Zika virus (ZIKV) is a mosquito-borne virus associated with neurological disorders such as Guillain-Barré syndrome and microcephaly. In humans, ZIKV is able to replicate in cell types from different tissues including placental cells, neurons, and microglia. This intricate virus-cell interaction is accompanied by virally induced changes in the infected cell aimed to promote viral replication as well as cellular responses aimed to counteract or tolerate the virus. Early in the infection, the 11-kb positive-sense RNA genome recruit ribosomes in the cytoplasm and the complex is translocated to the endoplasmic reticulum (ER) for viral protein synthesis. In this process, ZIKV replication is known to induce cellular stress, which triggers both the expression of innate immune genes and the phosphorylation of eukaryotic translation initiation factor 2 (eIF2α), shutting-off host protein synthesis. Remodeling of the ER during ZIKV replication also triggers the unfolded protein response (UPR), which induces changes in the cellular transcriptional landscapes aimed to tolerate infection or trigger apoptosis. Alternatively, ZIKV replication induces changes in the adenosine methylation patterns of specific host mRNAs, which have different consequences in viral replication and cellular fate. In addition, the ZIKV RNA genome undergoes adenosine methylation by the host machinery, which results in the inhibition of viral replication. However, despite these relevant findings, the full scope of these processes to the outcome of infection remains poorly elucidated. This review summarizes relevant aspects of the complex crosstalk between RNA metabolism and cellular stress responses against ZIKV and discusses their possible impact on viral pathogenesis.
PubMed: 32106582
DOI: 10.3390/pathogens9030158 -
Cells Apr 2021Here, we have attempted to address the timing of EV and virion release from virally infected cells. Uninfected (CEM), HIV-1-infected (J1.1), and human T cell leukemia...
Here, we have attempted to address the timing of EV and virion release from virally infected cells. Uninfected (CEM), HIV-1-infected (J1.1), and human T cell leukemia virus-1 (HTLV-1)-infected (HUT102) cells were synchronized in G. Viral latency was reversed by increasing gene expression with the addition of serum-rich media and inducers. Supernatants and cell pellets were collected post-induction at different timepoints and assayed for extracellular vesicle (EV) and autophagy markers; and for viral proteins and RNAs. Tetraspanins and autophagy-related proteins were found to be differentially secreted in HIV-1- and HTLV-1-infected cells when compared with uninfected controls. HIV-1 proteins were present at 6 h and their production increased up to 24 h. HTLV-1 proteins peaked at 6 h and plateaued. HIV-1 and HTLV-1 RNA production correlated with viral protein expression. Nanoparticle tracking analysis (NTA) showed increase of EV concentration over time in both uninfected and infected samples. Finally, the HIV-1 supernatant from the 6-h samples was found not to be infectious; however, the virus from the 24-h samples was successfully rescued and infectious. Overall, our data indicate that EV release may occur prior to viral release from infected cells, thereby implicating a potentially significant effect of EVs on uninfected recipient cells prior to subsequent viral infection and spread.
Topics: Apoptosis; Biomarkers; Cell Line; Culture Media, Conditioned; Cytokines; Extracellular Vesicles; HIV Infections; HIV-1; HTLV-I Infections; Human T-lymphotropic virus 1; Humans; Models, Biological; Myeloid Cells; RNA, Viral; T-Lymphocytes; Virion
PubMed: 33916140
DOI: 10.3390/cells10040781 -
Clinical and Experimental Medicine May 2024The ubiquitous RNA-processing molecule TDP-43 is involved in neuromuscular diseases such as inclusion body myositis, a late-onset acquired inflammatory myopathy. TDP-43... (Review)
Review
The ubiquitous RNA-processing molecule TDP-43 is involved in neuromuscular diseases such as inclusion body myositis, a late-onset acquired inflammatory myopathy. TDP-43 solubility and function are disrupted in certain viral infections. Certain viruses, high viremia, co-infections, reactivation of latent viruses, and post-acute expansion of cytotoxic T cells may all contribute to inclusion body myositis, mainly in an age-shaped immune landscape. The virally induced senescent, interferon gamma-producing cytotoxic CD8+ T cells with increased inflammatory, and cytotoxic features are involved in the occurrence of inclusion body myositis in most such cases, in a genetically predisposed host. We discuss the putative mechanisms linking inclusion body myositis, TDP-43, and viral infections untangling the links between viruses, interferon, and neuromuscular degeneration could shed a light on the pathogenesis of the inclusion body myositis and other TDP-43-related neuromuscular diseases, with possible therapeutic implications.
Topics: Myositis, Inclusion Body; Humans; Virus Diseases; DNA-Binding Proteins
PubMed: 38693436
DOI: 10.1007/s10238-024-01353-9 -
Gene Therapy May 2024In this study, we demonstrate the safety and utility of CRISPR-Cas9 gene editing technology for in vivo editing of proviral DNA in ART-treated, virally controlled simian...
In this study, we demonstrate the safety and utility of CRISPR-Cas9 gene editing technology for in vivo editing of proviral DNA in ART-treated, virally controlled simian immunodeficiency virus (SIV) infected rhesus macaques, an established model for HIV infection. EBT-001 is an AAV9-based vector delivering SaCas9 and dual guide RNAs designed to target multiple regions of the SIV genome: the viral LTRs, and the Gag gene. The results presented here demonstrate that a single IV inoculation of EBT-001 at each of 3 dose levels (1.4 × 10, 1.4 × 10 and 1.4 × 10 genome copies/kg) resulted in broad and functional biodistribution of AAV9-EBT-001 to known tissue reservoirs of SIV. No off-target effects or abnormal pathology were observed, and animals returned to their normal body weight after receiving EBT-001. Importantly, the macaques that received the 2 highest doses of EBT-001 showed improved absolute lymphocyte counts as compared to antiretroviral-treated controls. Taken together, these results demonstrate safety, biodistribution, and in vivo proviral DNA editing following IV administration of EBT-001, supporting the further development of CRISPR-based gene editing as a potential therapeutic approach for HIV in humans.
Topics: Animals; Simian Immunodeficiency Virus; Macaca mulatta; Gene Editing; CRISPR-Cas Systems; Simian Acquired Immunodeficiency Syndrome; Tissue Distribution; Genetic Vectors; Genetic Therapy; Dependovirus
PubMed: 37587230
DOI: 10.1038/s41434-023-00410-4 -
Viruses Sep 2019Precision genome engineering by CRISPR is a game-changing technology that originates from the study of virus-host interaction and promises to revolutionize virology and...
Precision genome engineering by CRISPR is a game-changing technology that originates from the study of virus-host interaction and promises to revolutionize virology and antiviral therapy [...].
Topics: CRISPR-Cas Systems; Clustered Regularly Interspaced Short Palindromic Repeats; Gene Editing; Genome, Viral; Host Microbial Interactions; Humans; Virology
PubMed: 31509984
DOI: 10.3390/v11090839 -
Current Opinion in Virology Dec 2021Meta-transcriptomic next-generation sequencing has transformed virus discovery, dramatically expanding our knowledge of the known virosphere. Nevertheless, the use of... (Review)
Review
Meta-transcriptomic next-generation sequencing has transformed virus discovery, dramatically expanding our knowledge of the known virosphere. Nevertheless, the use of meta-transcriptomics for virus discovery faces important challenges. As this technology becomes more widely adopted, the proportion of viral sequences in public databases with incorrect (e.g. mis-assignment of host) or limited information (e.g. lacking taxonomic classification) is likely to grow, limiting their utility in bioinformatic pipelines for virus discovery. In addition, we currently lack the bioinformatic tools that can accurately identify viruses showing little or no sequence similarity to database viruses or those that represent likely reagent contaminants. Herein, we outline some of the challenges to effective meta-transcriptomic virus discovery as well as their potential solutions.
Topics: Computational Biology; Gene Expression Regulation, Viral; High-Throughput Nucleotide Sequencing; Transcriptome; Virology; Viruses
PubMed: 34592710
DOI: 10.1016/j.coviro.2021.09.007 -
Viruses Nov 2021Paradigm shifts throughout the history of microbiology have typically been ignored, or met with skepticism and resistance, by the scientific community. This has been... (Review)
Review
Paradigm shifts throughout the history of microbiology have typically been ignored, or met with skepticism and resistance, by the scientific community. This has been especially true in the field of virology, where the discovery of a "", or infectious fluid remaining after excluding bacteria by filtration, was initially ignored because it did not coincide with the established view of microorganisms. Subsequent studies on such infectious agents, eventually termed "viruses", were met with skepticism. However, after an abundance of proof accumulated, viruses were eventually acknowledged as defined microbiological entities. Next, the proposed role of viruses in oncogenesis in animals was disputed, as was the unique mechanism of genome replication by reverse transcription of RNA by the retroviruses. This same pattern of skepticism holds true for the prediction of the existence of retroviral "antisense" transcripts and genes. From the time of their discovery, it was thought that retroviruses encoded proteins on only one strand of proviral DNA. However, in 1988, it was predicted that human immunodeficiency virus type 1 (HIV-1), and other retroviruses, express an antisense protein encoded on the DNA strand opposite that encoding the known viral proteins. Confirmation came quickly with the characterization of the antisense protein, HBZ, of the human T-cell leukemia virus type 1 (HTLV-1), and the finding that both the protein and its antisense mRNA transcript play key roles in viral replication and pathogenesis. However, acceptance of the existence, and potential importance, of a corresponding antisense transcript and protein (ASP) in HIV-1 infection and pathogenesis has lagged, despite gradually accumulating theoretical and experimental evidence. The most striking theoretical evidence is the finding that is highly conserved in group M viruses and correlates exclusively with subtypes, or clades, responsible for the AIDS pandemic. This review outlines the history of the major shifts in thought pertaining to the nature and characteristics of viruses, and in particular retroviruses, and details the development of the hypothesis that retroviral antisense transcripts and genes exist. We conclude that there is a need to accelerate studies on ASP, and its transcript(s), with the view that both may be important, and overlooked, targets in anti-HIV therapeutic and vaccine strategies.
Topics: Carcinogenesis; Genome, Viral; HIV-1; History, 20th Century; History, 21st Century; Human Immunodeficiency Virus Proteins; Human T-lymphotropic virus 1; Humans; Open Reading Frames; RNA, Antisense; RNA, Messenger; Retroviridae; Retroviridae Proteins; Transcription, Genetic; Viral Envelope Proteins; Virology; Virus Replication
PubMed: 34835027
DOI: 10.3390/v13112221