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Viruses May 2024The hepatitis B virus (HBV) infects hepatocytes and hijacks host cellular mechanisms for its replication. Host proteins can be frontline effectors of the cell's defense... (Review)
Review
The hepatitis B virus (HBV) infects hepatocytes and hijacks host cellular mechanisms for its replication. Host proteins can be frontline effectors of the cell's defense and restrict viral replication by impeding multiple steps during its intracellular lifecycle. This review summarizes many of the well-described restriction factors, their mechanisms of restriction, and counteractive measures of HBV, with a special focus on viral transcription. We discuss some of the limitations and knowledge gaps about the restriction factors, highlighting how these factors may be harnessed to facilitate therapeutic strategies against HBV.
Topics: Hepatitis B virus; Virus Replication; Humans; Host-Pathogen Interactions; Hepatitis B; Hepatocytes; Animals
PubMed: 38793645
DOI: 10.3390/v16050764 -
International Journal of Molecular... Jun 2024The respiratory system is constantly exposed to viral infections that are responsible for mild to severe diseases. In this narrative review, we focalized the attention... (Review)
Review
The respiratory system is constantly exposed to viral infections that are responsible for mild to severe diseases. In this narrative review, we focalized the attention on (RSV), influenza virus, and (SARS-CoV-2) infections, responsible for high morbidity and mortality in the last decades. We reviewed the human innate and adaptive immune responses in the airways following infection, focusing on a particular population: newborns and pregnant women. The recent Coronavirus disease-2019 (COVID-19) pandemic has highlighted how our interest in viral pathologies must not decrease. Furthermore, we must increase our knowledge of infection mechanisms to improve our future defense strategies.
Topics: Humans; COVID-19; Respiratory Tract Infections; Pregnancy; SARS-CoV-2; Respiratory Syncytial Virus Infections; Female; Immunity, Innate; Adaptive Immunity; Infant, Newborn; Influenza, Human; Virus Diseases
PubMed: 38892370
DOI: 10.3390/ijms25116178 -
Journal of Virology Sep 2023Bats carry genetically diverse severe acute respiratory syndrome-related coronaviruses (SARSr-CoVs). Some of them utilize human angiotensin-converting enzyme 2 (hACE2)...
Bats carry genetically diverse severe acute respiratory syndrome-related coronaviruses (SARSr-CoVs). Some of them utilize human angiotensin-converting enzyme 2 (hACE2) as a receptor and cannot efficiently replicate in wild-type mice. Our previous study demonstrated that the bat SARSr-CoV rRsSHC014S induces respiratory infection and lung damage in hACE2 transgenic mice but not wild-type mice. In this study, we generated a mouse-adapted strain of rRsSHC014S, which we named SMA1901, by serial passaging of wild-type virus in BALB/c mice. SMA1901 showed increased infectivity in mouse lungs and induced interstitial lung pneumonia in both young and aged mice after intranasal inoculation. Genome sequencing revealed mutations in not only the spike protein but the whole genome, which may be responsible for the enhanced pathogenicity of SMA1901 in wild-type BALB/c mice. SMA1901 induced age-related mortality similar to that observed in SARS and COVID-19. Drug testing using antibodies and antiviral molecules indicated that this mouse-adapted virus strain can be used to test prophylactic and therapeutic drug candidates against SARSr-CoVs. IMPORTANCE The genetic diversity of SARSr-CoVs in wildlife and their potential risk of cross-species infection highlights the importance of developing a powerful animal model to evaluate the antibodies and antiviral drugs. We acquired the mouse-adapted strain of a bat-origin coronavirus named SMA1901 by natural serial passaging of rRsSHC014S in BALB/c mice. The SMA1901 infection caused interstitial pneumonia and inflammatory immune responses in both young and aged BALB/c mice after intranasal inoculation. Our model exhibited age-related mortality similar to SARS and COVID-19. Therefore, our model will be of high value for investigating the pathogenesis of bat SARSr-CoVs and could serve as a prospective test platform for prophylactic and therapeutic candidates.
Topics: Animals; Mice; Chiroptera; Severe acute respiratory syndrome-related coronavirus; Mice, Inbred BALB C; COVID-19; Severe Acute Respiratory Syndrome; Serial Passage; Antiviral Agents; Antibodies, Viral; Viral Zoonoses; Lung Diseases, Interstitial; Aging; Drug Evaluation, Preclinical
PubMed: 37607058
DOI: 10.1128/jvi.00790-23 -
The Journal of Cell Biology Jul 2023Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the etiologic agent for the global COVID-19 pandemic, triggers the formation of endoplasmic reticulum...
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the etiologic agent for the global COVID-19 pandemic, triggers the formation of endoplasmic reticulum (ER)-derived replication organelles, including double-membrane vesicles (DMVs), in the host cell to support viral replication. Here, we clarify how SARS-CoV-2 hijacks host factors to construct the DMVs. We show that the ER morphogenic proteins reticulon-3 (RTN3) and RTN4 help drive DMV formation, enabling viral replication, which leads to productive infection. Different SARS-CoV-2 variants, including the delta variant, use the RTN-dependent pathway to promote infection. Mechanistically, our results reveal that the membrane-embedded reticulon homology domain (RHD) of the RTNs is sufficient to functionally support viral replication and physically engage NSP3 and NSP4, two viral non-structural membrane proteins known to induce DMV formation. Our findings thus identify the ER morphogenic RTN3 and RTN4 membrane proteins as host factors that help promote the biogenesis of SARS-CoV-2-induced DMVs, which can act as viral replication platforms.
Topics: Humans; COVID-19; Endoplasmic Reticulum; Membrane Proteins; Pandemics; SARS-CoV-2; Virus Replication; Organelles; Viral Nonstructural Proteins
PubMed: 37093123
DOI: 10.1083/jcb.202203060 -
Nature Communications Dec 2023Zika virus (ZIKV) has emerged as a global health issue, yet neither antiviral therapy nor a vaccine are available. ZIKV is an enveloped RNA virus, replicating in the...
Zika virus (ZIKV) has emerged as a global health issue, yet neither antiviral therapy nor a vaccine are available. ZIKV is an enveloped RNA virus, replicating in the cytoplasm in close association with ER membranes. Here, we isolate ER membranes from ZIKV-infected cells and determine their proteome. Forty-six host cell factors are enriched in ZIKV remodeled membranes, several of these having a role in redox and methylation pathways. Four proteins are characterized in detail: thioredoxin reductase 1 (TXNRD1) contributing to folding of disulfide bond containing proteins and modulating ZIKV secretion; aldo-keto reductase family 1 member C3 (AKR1C3), regulating capsid protein abundance and thus, ZIKV assembly; biliverdin reductase B (BLVRB) involved in ZIKV induced lipid peroxidation and increasing stability of viral transmembrane proteins; adenosylhomocysteinase (AHCY) indirectly promoting mA methylation of ZIKV RNA by decreasing the level of S- adenosyl homocysteine and thus, immune evasion. These results highlight the involvement of redox and methylation enzymes in the ZIKV life cycle and their accumulation at virally remodeled ER membranes.
Topics: Humans; Zika Virus; Zika Virus Infection; Methylation; Proviruses; Virus Replication; Viral Proteins; Oxidation-Reduction
PubMed: 38052817
DOI: 10.1038/s41467-023-43665-6 -
Journal of Translational Medicine Oct 2023Myalgic encephalitis/chronic fatigue syndrome (ME/CFS) is a long-term disabling illness without a medically explained cause. Recently during COVID-19 pandemic, many... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Myalgic encephalitis/chronic fatigue syndrome (ME/CFS) is a long-term disabling illness without a medically explained cause. Recently during COVID-19 pandemic, many studies have confirmed the symptoms similar to ME/CFS in the recovered individuals. To investigate the virus-related etiopathogenesis of ME/CFS, we conducted a systematic assessment of viral infection frequency in ME/CFS patients.
METHODS
We conducted a comprehensive search of PubMed and the Cochrane Library from their inception through December 31, 2022, using selection criteria of viral infection prevalence in ME/CFS patients and controls. Subsequently, we performed a meta-analysis to assess the extent of viral infections' contribution to ME/CFS by comparing the odds ratio between ME/CFS patients and controls (healthy and/or diseased).
RESULTS
Finally, 64 studies met our eligibility criteria regarding 18 species of viruses, including a total of 4971 ME/CFS patients and 9221 control subjects. The participants included healthy subjects and individuals with one of 10 diseases, such as multiple sclerosis or fibromyalgia. Two DNA viruses (human herpes virus (HHV)-7 and parvovirus B19, including their co-infection) and 3 RNA viruses (borna disease virus (BDV), enterovirus and coxsackie B virus) showed odds ratios greater than 2.0 compared with healthy and/or diseased subjects. Specifically, BDV exceeded the cutoff with an odds ratio of ≥ 3.47 (indicating a "moderate association" by Cohen's d test) compared to both healthy and diseased controls.
CONCLUSION
This study comprehensively evaluated the risk of viral infections associated with ME/CFS, and identified BDV. These results provide valuable reference data for future studies investigating the role of viruses in the causation of ME/CFS.
Topics: Humans; Encephalitis; Fatigue Syndrome, Chronic; Fibromyalgia; Virus Diseases
PubMed: 37898798
DOI: 10.1186/s12967-023-04635-0 -
Viruses May 2024Papillomavirus gene regulation is largely post-transcriptional due to overlapping open reading frames and the use of alternative polyadenylation and alternative splicing... (Review)
Review
Papillomavirus gene regulation is largely post-transcriptional due to overlapping open reading frames and the use of alternative polyadenylation and alternative splicing to produce the full suite of viral mRNAs. These processes are controlled by a wide range of cellular RNA binding proteins (RPBs), including constitutive splicing factors and cleavage and polyadenylation machinery, but also factors that regulate these processes, for example, SR and hnRNP proteins. Like cellular RNAs, papillomavirus RNAs have been shown to bind many such proteins. The life cycle of papillomaviruses is intimately linked to differentiation of the epithelial tissues the virus infects. For example, viral late mRNAs and proteins are expressed only in the most differentiated epithelial layers to avoid recognition by the host immune response. Papillomavirus genome replication is linked to the DNA damage response and viral chromatin conformation, processes which also link to RNA processing. Challenges with respect to elucidating how RBPs regulate the viral life cycle include consideration of the orchestrated spatial aspect of viral gene expression in an infected epithelium and the epigenetic nature of the viral episomal genome. This review discusses RBPs that control viral gene expression, and how the connectivity of various nuclear processes might contribute to viral mRNA production.
Topics: RNA-Binding Proteins; Humans; Gene Expression Regulation, Viral; RNA, Viral; Papillomaviridae; Virus Replication; Viral Proteins; Papillomavirus Infections; Genome, Viral; Host-Pathogen Interactions; RNA, Messenger
PubMed: 38793664
DOI: 10.3390/v16050783 -
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 -
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