-
Kidney International Nov 2023In the modern era, it is unknown if people that are virally suppressed with HIV (PWH) are at increased risk for acute kidney injury (AKI) compared to people without HIV...
In the modern era, it is unknown if people that are virally suppressed with HIV (PWH) are at increased risk for acute kidney injury (AKI) compared to people without HIV and no studies have compared the risk of AKI by viral suppression status. Here, we determined the associations of HIV status and AKI among PWH with and without viral suppression compared to people without HIV. An observational cohort study of PWH and people without HIV hospitalized in a large New York City health system between 2010-2019 was conducted. Multivariable Cox proportional hazards models were used to determine associations between HIV status and risk of AKI, severe AKI and development of chronic kidney disease (CKD). Among 173,884 hospitalized patients, 4,718 had HIV; 2,532 (53.7%) were virally suppressed and 2,186 (46.3%) were not suppressed. Compared to people without HIV, PWH with and without viral suppression were at increased risk of AKI (adjusted hazard ratio 1.27, 95% confidence interval 1.15, 1.40 and 1.73, 1.58, 1.90, respectively) and AKI requiring kidney replacement therapy (1.89, 1.27, 2.84 and 1.87, 1.23, 2.84, respectively). Incremental, graded associations were observed between HIV status and Stage 2 or 3 AKI, and among AKI survivors, and incident CKD. The elevated risk of AKI across ages of PWH was similar in magnitude to older people without HIV. Thus, regardless of virologic control, HIV is an independent risk factor for AKI among hospitalized patients. Future studies should determine the mechanisms by which HIV increases susceptibility to AKI and identify strategies to prevent AKI in PWH.
PubMed: 37598853
DOI: 10.1016/j.kint.2023.07.022 -
Journal of Virology Oct 2023This study highlights the crucial role RNA processing plays in regulating viral gene expression and replication. By targeting SR kinases, we identified harmine as a...
This study highlights the crucial role RNA processing plays in regulating viral gene expression and replication. By targeting SR kinases, we identified harmine as a potent inhibitor of HIV-1 as well as coronavirus (HCoV-229E and multiple SARS-CoV-2 variants) replication. Harmine inhibits HIV-1 protein expression and reduces accumulation of HIV-1 RNAs in both cell lines and primary CD4 T cells. Harmine also suppresses coronavirus replication post-viral entry by preferentially reducing coronavirus sub-genomic RNA accumulation. By focusing on host factors rather than viral targets, our study offers a novel approach to combating viral infections that is effective against a range of unrelated viruses. Moreover, at doses required to inhibit virus replication, harmine had limited toxicity and minimal effect on the host transcriptome. These findings support the viability of targeting host cellular processes as a means of developing broad-spectrum anti-virals.
Topics: Humans; Antiviral Agents; Coronavirus; Coronavirus Infections; Harmine; HIV-1; Virus Replication
PubMed: 37706687
DOI: 10.1128/jvi.00396-23 -
BioRxiv : the Preprint Server For... Nov 2023The 40-50 RNA modifications of the epitranscriptome regulate posttranscriptional gene expression. Here we show that flaviviruses hijack the host tRNA epitranscriptome to...
The 40-50 RNA modifications of the epitranscriptome regulate posttranscriptional gene expression. Here we show that flaviviruses hijack the host tRNA epitranscriptome to promote expression of pro-viral proteins, with tRNA-modifying ALKBH1 acting as a host restriction factor in dengue virus infection. Early in the infection of human Huh-7 cells, ALKBH1 and its tRNA products 5-formylcytidine (fC) and 2'--methyl-5-formylcytidine (fCm) were reduced. ALKBH1 knockdown mimicked viral infection, but caused increased viral NS3 protein levels during infection, while ALKBH1 overexpression reduced NS3 levels and viral replication, and increased fC and fCm. Viral NS5, but not host FTSJ1, increased fCm levels late in infection. Consistent with reports of impaired decoding of leucine UUA codon by fCm-modified tRNA, ALKBH1 knockdown induced translation of UUA-deficient transcripts, most having pro-viral functions. Our findings support a dynamic ALKBH1/fCm axis during dengue infection, with virally-induced remodeling of the proteome by tRNA reprogramming and codon-biased translation.
PubMed: 37986976
DOI: 10.1101/2023.11.05.565734 -
Methods in Molecular Biology (Clifton,... 2024Vectored RNA vaccines offer a variety of possibilities to engineer targeted vaccines. They are cost-effective and safe, but replication competent, activating the humoral... (Review)
Review
Vectored RNA vaccines offer a variety of possibilities to engineer targeted vaccines. They are cost-effective and safe, but replication competent, activating the humoral as well as the cellular immune system.This chapter focuses on RNA vaccines derived from negative-strand RNA viruses from the order Mononegavirales with special attention to Newcastle disease virus-based vaccines and their generation. It shall provide an overview on the advantages and disadvantages of certain vector platforms as well as their scopes of application, including an additional section on experimental COVID-19 vaccines.
Topics: Animals; Humans; COVID-19; Genetic Vectors; Newcastle disease virus; RNA Viruses; SARS-CoV-2; Viral Vaccines; mRNA Vaccines
PubMed: 38814390
DOI: 10.1007/978-1-0716-3770-8_3 -
Cell Host & Microbe Jun 2024In this issue of Cell Host & Microbe, Shang et al. identify murine neuropilin 1 as a host factor that binds reovirus particles, directing cell entry and contributing to...
In this issue of Cell Host & Microbe, Shang et al. identify murine neuropilin 1 as a host factor that binds reovirus particles, directing cell entry and contributing to viral dissemination and neurovirulence. This study highlights the reovirus model system to investigate host receptors and their significance in viral pathogenesis.
Topics: Animals; Mice; Neurons; Neuropilin-1; Reoviridae; Virus Internalization; Humans; Host-Pathogen Interactions; Reoviridae Infections; Receptors, Virus
PubMed: 38870904
DOI: 10.1016/j.chom.2024.05.013 -
Tumour Virus Research Dec 2023Approximately 20 % of human cancers are associated with virus infection. DNA tumor viruses can induce tumor formation in host cells by disrupting the cell's DNA... (Review)
Review
Approximately 20 % of human cancers are associated with virus infection. DNA tumor viruses can induce tumor formation in host cells by disrupting the cell's DNA replication and repair mechanisms. Specifically, these viruses interfere with the host cell's DNA damage response (DDR), which is a complex network of signaling pathways that is essential for maintaining the integrity of the genome. DNA tumor viruses can disrupt these pathways by expressing oncoproteins that mimic or inhibit various DDR components, thereby promoting genomic instability and tumorigenesis. Recent studies have highlighted the molecular mechanisms by which DNA tumor viruses interact with DDR components, as well as the ways in which these interactions contribute to viral replication and tumorigenesis. Understanding the interplay between DNA tumor viruses and the DDR pathway is critical for developing effective strategies to prevent and treat virally associated cancers. In this review, we discuss the current state of knowledge regarding the mechanisms by which human papillomavirus (HPV), merkel cell polyomavirus (MCPyV), Kaposi's sarcoma-associated herpesvirus (KSHV), and Epstein-Barr virus (EBV) interfere with DDR pathways to facilitate their respective life cycles, and the consequences of such interference on genomic stability and cancer development.
Topics: Humans; Epstein-Barr Virus Infections; Herpesvirus 4, Human; DNA Tumor Viruses; Neoplasms; Herpesvirus 8, Human; DNA Repair; Carcinogenesis
PubMed: 37918513
DOI: 10.1016/j.tvr.2023.200272 -
Genes & Diseases Nov 2023Virus-related cancer is cancer where viral infection leads to the malignant transformation of the host's infected cells. Seven viruses (e.g., human papillomavirus (HPV),... (Review)
Review
Virus-related cancer is cancer where viral infection leads to the malignant transformation of the host's infected cells. Seven viruses (e.g., human papillomavirus (HPV), Epstein-Barr virus (EBV), Kaposi's sarcoma herpesvirus (KSHV), Hepatitis B virus (HBV), Hepatitis C virus (HCV), Human T-lymphotropic virus (HTLV), and Merkel cell polyomavirus (MCV)) that infect humans have been identified as an oncogene and have been associated with several human malignancies. Recently, growing attention has been attracted to exploring the pathogenesis of virus-related cancers. One of the most mysterious molecules involved in carcinogenesis and progression of virus-related cancers is circular RNAs (circRNA). These emerging non-coding RNAs (ncRNAs), due to the absence of 5' and 3' ends, have high stability than linear RNAs and are found in some species across the eukaryotic organisms. Compelling evidence has revealed that viruses also encode a repertoire of circRNAs, as well as dysregulation of these viral circRNAs play a critical role in the pathogenesis and progression of different types of virus-related cancers. Therefore, understanding the exact role and function of the virally encoded circRNAs with virus-associated cancers will open a new road for increasing our knowledge about the RNA world. Hence, in this review, we will focus on emerging roles of virus-encoded circRNAs in multiple cancers, including cervical cancer, gastric cancer, Merkel cell carcinoma, nasopharyngeal carcinoma, Kaposi cancer, and liver cancer.
PubMed: 37554189
DOI: 10.1016/j.gendis.2022.04.009 -
Reviews in Medical Virology May 2024The viral infection of the central nervous system is a significant public health concern. So far, most clinical cases of viral neuroinvasion are dealt with supportive... (Review)
Review
The viral infection of the central nervous system is a significant public health concern. So far, most clinical cases of viral neuroinvasion are dealt with supportive and/or symptomatic treatments due to the unavailability of specific treatments. Thus, developing specific therapies is required to alleviate neurological symptoms and disorders. In this review, we shed light on molecular aspects of viruses' entry into the brain which upon targeting with specific drugs have shown promising efficacy in vitro and in preclinical in vivo model systems. Further assessing the therapeutic potential of these drugs in clinical trials may offer opportunities to halt viral neuroinvasion in humans.
Topics: Humans; Animals; Antiviral Agents; Virus Internalization; Brain; Central Nervous System Viral Diseases
PubMed: 38719789
DOI: 10.1002/rmv.2539 -
Comparative Immunology, Microbiology... Jun 2024Henipavirus (HNV) is well known for two zoonotic viruses in the genus, Hendra virus (HeV) and Nipah virus (NiV), which pose serious threat to human and animal health. In... (Review)
Review
Henipavirus (HNV) is well known for two zoonotic viruses in the genus, Hendra virus (HeV) and Nipah virus (NiV), which pose serious threat to human and animal health. In August 2022, a third zoonotic virus in the genus Henipavirus, Langya virus (LayV), was discovered in China. The emergence of HeV, NiV, and LayV highlights the persistent threat of HNV to human and animal health. In addition to the above three HNVs, new species within this genus are still being discovered. Although they have not yet caused a pandemic in humans or livestock, they still have the risk of spillover as a potential threat to the health of humans and animals. It's important to understand the infection and transmission of different HNV in animals for the prevention and control of current or future HNV epidemics. Therefore, this review mainly summarizes the animal origin, animal infection and transmission of HNV that have been found worldwide, and further analyzes and summarizes the rules of infection and transmission, so as to provide a reference for relevant scientific researchers. Furthermore, it can provide a direction for epidemic prevention and control, and animal surveillance to reduce the risk of the global pandemic of HNV.
Topics: Animals; Henipavirus Infections; Henipavirus; Humans; Zoonoses; Viral Zoonoses; Nipah Virus; Hendra Virus
PubMed: 38640700
DOI: 10.1016/j.cimid.2024.102183 -
British Journal of Haematology Sep 2023High rates of lung failure have been reported in haematological patients after SARS-CoV2 infection. An early administration of monoclonal antibodies or anti-virals may...
High rates of lung failure have been reported in haematological patients after SARS-CoV2 infection. An early administration of monoclonal antibodies or anti-virals may improve the prognosis. Oral anti-virals may have a wider use independently of the genetic variations of the virus. Prospective data on anti-virals in haematological malignancies (HMs) are still lacking. Outpatients diagnosed with HM and early COVID-19 infection were prospectively treated with the oral anti-virals nirmatrelvir/ritonavir and molnupiravir. Incidence of lung failure, deaths and adverse events was analysed. Long-term outcome at third month was evaluated. Eighty-two outpatients were evaluable for the study objectives. All patients had been treated for their HM within 12 months. COVID-19-related lung failure was 23.1%. Active HM (aOR = 4.42; p = 0.038) and prolonged viral shedding (aOR = 1.04; p = 0.022) resulted independent predictors of severe infection. The vaccination with three to four doses (aOR = 0.02; p = 0.001) and with two doses (aOR = 0.06; p = 0.006) resulted protective. COVID-19-related deaths at 28 days were 6.1%. All-cause mortality at 90-day follow-up was 13.4% (n. 11) and included opportunistic infections and cardiovascular events. In conclusion, this approach reduced the incidence of lung failure and specific mortality compared to previous cohorts, but patients remain at high risk of further complications.
Topics: Humans; Prospective Studies; RNA, Viral; COVID-19; SARS-CoV-2; Hematologic Neoplasms; Antiviral Agents
PubMed: 37259629
DOI: 10.1111/bjh.18895