Viral Proliferation Research Articles

Bombyx mori C-Type Lectin (BmIML-2) Inhibits the Proliferation of B. mori Nucleopolyhedrovirus (BmNPV) through Involvement in Apoptosis.

C-type lectins (CTLs) are widely distributed in mammals, insects, and plants, which act as pattern recognition receptors (PRRs) to recognize pathogens and initiate immune responses. In this study, we identified a C-type lectin gene called BmIML-2 from the silkworm Bombyx mori. Its open reading frame (ORF) encodes 314 amino acids, which contain dual tandem C-type lectin-like domain (CTLD). BmIML-2 is highly expressed in the fat body and is significantly induced at 24 h after BmNPV infection. Moreover, overexpression of BmIML-2 dramatically inhibited the proliferation of BmNPV, and knockdown assay via siRNA further validated the inhibition of BmIML-2 on viral proliferation. In addition, transcript level detection of apoptosis-related genes and observation of apoptosis bodies implied that overexpression of BmIML-2 promoted BmNPV-induced apoptosis. Immunofluorescence analysis indicated that BmIML-2 distributed throughout the cytoplasm and was slightly concentrated in the cell membrane. Taken together, our results suggest that BmIML-2 could inhibit in the proliferation of BmNPV by facilitating cell apoptosis.

Deep Content Information Retrieval for COVID-19 Detection from Chromatic CT Scans.

In this paper, we investigate the role of the chromatic information in CT scans in COVID-19 detection and we aim to confirm the inclusion of the artificial intelligence findings in assisting COVID-19 diagnosis. This paper proposes a freezing-based convolutional neural network learning using a morphological transformation of CT images to classify COVID-19 cohorts to help in prognostication pneumonia disease monitoring. The experiments made on the collected CT images from previous works have proven to be a powerful aid to recognize the lesions in CT images which works at comprehensively greater accuracy and speed. The proposed CNN architecture has reflected the viral proliferation in infected patients and archives an accuracy of 87.56% with an improvement by 3% compared to the baseline method on the available database of CT images.

PSMD12-Mediated M1 Ubiquitination of Influenza A Virus at K102 Regulates Viral Replication.

ABSTRACTThe M1 of influenza A virus (IAV) is important for the virus life cycle, especially for the assembly and budding of viruses, which is a multistep process that requires host factors. Identifying novel host proteins that interact with M1 and understanding their functions in IAV replication are of great interest in antiviral drug development. In this study, we identified 19 host proteins in DF1 cells suspected to interact with the M1 protein of an H5N6 virus through immunoprecipitation (IP)/mass spectrometry. Among them, PSMD12, a 26S proteasome regulatory subunit, was shown to interact with influenza M1, acting as a positive host factor in IAV replication in avian and human cells. The data showed that PSMD12 promoted K63-linked ubiquitination of M1 at the K102 site. H5N6 and PR8 with an M1-K102 site mutant displayed a significantly weaker replication ability than the wild-type viruses. Mechanistically, PSMD12 promoted M1-M2 virus-like particle (VLP) release, and an M1-K102 mutation disrupted the formation of supernatant M1-M2 VLPs. An H5N6 M1-K102 site mutation or knockdown PSMD12 disrupted the budding release of the virus in chicken embryo fibroblast (CEF) cells, which was confirmed by transmission electron microscopy. Further study confirmed that M1-K102 site mutation significantly affected the virulence of H5N6 and PR8 viruses in mice. In conclusion, we report the novel host factor PSMD12 which affects the replication of influenza virus by mediating K63-linked ubiquitination of M1 at K102. These findings provide novel insight into the interactions between IAV and host cells, while suggesting an important target for anti-influenza virus drug research.IMPORTANCE M1 is proposed to play multiple biologically important roles in the life cycle of IAV, which relies largely on host factors. This study is the first one to identify that PSMD12 interacts with M1, mediates K63-linked ubiquitination of M1 at the K102 site, and thus positively regulates influenza virus proliferation. PSMD12 promoted M1-M2 VLP egress, and an M1-K102 mutation affected the M1-M2 VLP formation. Furthermore, we demonstrate the importance of this site to the morphology and budding of influenza viruses by obtaining mutant viruses, and the M1 ubiquitination regulator PSMD12 has a similar function to the M1 K102 mutation in regulating virus release and virus morphology. Additionally, we confirm the reduced virulence of H5N6 and PR8 (H1N1) viruses carrying the M1-K102 site mutation in mice. These findings provide novel insights into IAV interactions with host cells and suggest a valid and highly conserved candidate target for antiviral drug development.

Inhibitory effects of cedar pine needle extract on H9N2 avian influenza virus in vitro and in vivo

H9N2 avian influenza virus causes significant economic losses to the poultry industry, due to its wide-spread prevalence and propensity to induce secondary and mixed infections. Antigenic drift limits vaccine efficacy. New anti-viral therapies are needed to complement existing control measures. At the maximum non-cytotoxic concentration (25 mg/mL), cedar pine needle extract inhibited H9N2 avian influenza virus proliferation in vitro and in vivo. Cedar pine needle extract reduced the haemagglutinin titre, inhibited H9N2 avian influenza virus nucleocapsid protein expression, and indirectly regulate type I and II interferon expression. Interleukin-6 expression increased during the pre-infection period but decreased during the mid-to-late stages of infection. Cedar pine needle extract may inhibit the proliferation of pathogens, regulate the immune response, and reduce host tissue damage and may serve as a potential target for drug development against H9N2 avian influenza virus.

Therapeutic Effects of a Dry Powder Prepared from the Green Microalga Coccomyxa sp. KJ in Mice Infected with Influenza A Virus

Influenza virus is a seasonal respiratory pathogen that produces global pandemics by genome reassortments. This rapid evolution creates difficulty in producing vaccines. Although several anti-influenza drugs have been developed, acquisition of rapid drug resistance by viruses is common. Therefore, it is important to develop novel therapeutic and prophylactic strategies. In this study, we evaluated the antiviral effects of a microalgae Coccomyxa sp. KJ (IPOD FERM BP-22254) extract in a BALB/c mouse model of influenza. Oral administration of dry algal powder (5 mg/day or 20 mg/day) before infection with influenza A virus (IFV) suppressed viral proliferation in the lungs and bronchoalveolar lavage fluid (BALF). It also exhibited stimulatory effects on systemic and local production of neutralizing antibodies. These results suggest that this powder is a promising candidate for the therapeutic and prophylactic management of influenza.

Molecular Mechanisms of the Medicines for COVID-19

Abstract For these three years, COVID-19 has globally spread and caused enormous damage all over the world. Although vaccines served to reduce its infection, their effects are still limited mainly due to rapid and vigorous mutations of SARS-CoV-2 virus. In order to bring this pandemic under control, we must develop novel medicines which are easily administered when needed and very effective without undesired side-effects. In this account, the developments of specific medicines for COVID-19 are surveyed with the emphasis on the molecular mechanisms of their therapeutic actions. Most of them are inhibitors of enzymes, which are indispensable for the virus, but unnecessary for human beings. These inhibitors selectively hamper the critical steps for viral proliferation (viral entry to human cells, replication of RNA genome, production of viral proteins, and others). There have been several successful examples, which are already approved as medicines for the treatment of COVID-19. Unfortunately, however, few of them sufficiently satisfy all the requirements to overcome this unprecedented pandemic completely, and thus further innovation is necessary.

Interaction between endogenous microRNAs and virus-derived small RNAs controls viral replication in insect vectors.

MicroRNAs (miRNAs) play an important role in resisting virus infection in insects. Viruses are recognized by insect RNA interference systems, which generate virus-derived small RNAs (vsRNAs). To date, it is unclear whether viruses employ vsRNAs to regulate the expression of endogenous miRNAs. We previously found that miR-263a facilitated the proliferation of rice stripe virus (RSV) in the insect vector small brown planthopper. However, miR-263a was significantly downregulated by RSV. Here, we deciphered the regulatory mechanisms of RSV on miR-263a expression. The promoter region of miR-263a was characterized, and the transcription factor YY1 was found to negatively regulate the transcription of miR-263a. The nucleocapsid protein of RSV promoted the inhibitory effect of YY1 on miR-263a transcription by reducing the binding ability of RNA polymerase II to the promoter of miR-263a. Moreover, an RSV-derived small RNA, vsR-3397, downregulated miR-263a transcription by directly targeting the promoter region with partial sequence complementarity. The reduction in miR-263a suppressed RSV replication and was beneficial for maintaining a tolerable accumulation level of RSV in insect vectors. This dual regulation mechanism reflects an ingenious adaptation strategy of viruses to their insect vectors.

Calcium Ions Signaling: Targets for Attack and Utilization by Viruses.

Calcium, as a second intracellular messenger, participate in various physiological and biochemical processes, including cell growth and proliferation, energy metabolism, information transfer, cell death, and immune response. Ca2+ channels or pumps in plasma and organelle membranes and Ca2+-related proteins maintain Ca2+ homeostasis by regulating Ca2+ inflow, outflow and buffering to avoid any adverse effects caused by Ca2+ overload or depletion. Thus, Ca2+ signaling also provides a target for virus invasion, replication, proliferation and release. After hijacking the host cell, viruses exploit Ca2+ signaling to regulate apoptosis and resist host immunity to establish persistent infection. In this review, we discuss cellular Ca2+ signaling and channels, interaction of calcium-associated proteins with viruses, and host cell fate, as well as the role of Ca2+ in cell death and antiviral response during viral infection.

Recent Progress in the Development of Opaganib for the Treatment of Covid-19.

The Covid-19 pandemic driven by the SARS-CoV-2 virus continues to exert extensive humanitarian and economic stress across the world. Although antivirals active against mild disease have been identified recently, new drugs to treat moderate and severe Covid-19 patients are needed. Sphingolipids regulate key pathologic processes, including viral proliferation and pathologic host inflammation. Opaganib (aka ABC294640) is a first-in-class clinical drug targeting sphingolipid metabolism for the treatment of cancer and inflammatory diseases. Recent work demonstrates that opaganib also has antiviral activity against several viruses including SARS-CoV-2. A recently completed multinational Phase 2/3 clinical trial of opaganib in patients hospitalized with Covid-19 demonstrated that opaganib can be safely administered to these patients, and more importantly, resulted in a 62% decrease in mortality in a large subpopulation of patients with moderately severe Covid-19. Furthermore, acceleration of the clearance of the virus was observed in opaganib-treated patients. Understanding the biochemical mechanism for the anti-SARS-CoV-2 activity of opaganib is essential for optimizing Covid-19 treatment protocols. Opaganib inhibits three key enzymes in sphingolipid metabolism: sphingosine kinase-2 (SK2); dihydroceramide desaturase (DES1); and glucosylceramide synthase (GCS). Herein, we describe a tripartite model by which opaganib suppresses infection and replication of SARS-CoV-2 by inhibiting SK2, DES1 and GCS. The potential impact of modulation of sphingolipid signaling on multi-organ dysfunction in Covid-19 patients is also discussed.

Multifaceted Roles of the E3 Ubiquitin Ligase RING Finger Protein 115 in Immunity and Diseases.

Ubiquitination is a post-translational modification that plays essential roles in various physiological and pathological processes. Protein ubiquitination depends on E3 ubiquitin ligases that catalyze the conjugation of ubiquitin molecules on lysine residues of targeted substrates. RING finger protein 115 (RNF115), also known as breast cancer associated gene 2 (BCA2) and Rab7-interacting RING finger protein (Rabring7), has been identified as a highly expressed protein in breast cancer cells and tissues. Later, it has been demonstrated that RNF115 catalyzes ubiquitination of a series of proteins to modulate a number of signaling pathways, and thereby regulates viral infections, autoimmunity, cell proliferation and death and tumorigenesis. In this review, we introduce the identification, expression and activity regulation of RNF115, summarize the substrates and functions of RNF115 in different pathways, and discuss the roles of RNF115 as a biomarker or therapeutic target in diseases.

Duck Plague Virus Negatively Regulates IFN Signaling to Promote Virus Proliferation via JNK Signaling Pathway.

Duck plague virus (DPV), a member of the alphaherpesvirus subfamily, can cause severe damage and immunosuppression in ducks and geese in China. Since lacking an available cell model, the antiviral signal transduction pathways induction and regulation mechanisms related to DPV infection in duck cells are still enigmatic. Our previous study developed a monocyte/macrophages cell model, which has been applied to study innate immunity with DPV. In the present study, we compared and analyzed transcriptome associated with the DPV infection of CHv (virulent strain) and CHa (avirulent strain) at 48hpi based on the duck monocyte/macrophages cell model and RNA-seq technology. Differentially expressed genes (DEGs) analysis showed 2,909 and 2,438 genes altered in CHv and CHa infected cells compared with control cells. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis showed that the DEGs were mainly involved in biological processes such as metabolic pathways, viral infectious diseases, immune system, and signal transduction. The CHv and CHa virus differentially regulated MAPK, NF-κB, and IFN signaling pathways based on transcriptome sequencing data and RT-qPCR results. The JNK inhibitor SP600125 enhanced the IFN signaling, but potentially reduced the VSV and DPV titers in the cell culture supernatant, indicating that JNK negatively regulates the IFN pathway and the inflammatory pathway to promote virus proliferation. The research results may provide promising information to understand the pathogenesis of DPV and provide a novel mechanism by which DPV modulates antiviral signaling and facilitate virus proliferation through hijacking the JNK pathway, which provides a new means for the prevention and control of DPV infection.

Construction of a Porcine Reproductive and Respiratory Syndrome Virus with Nanoluc Luciferase Reporter: a Stable and Highly Efficient Tool for Viral Quantification Both In Vitro and In Vivo.

ABSTRACTPorcine reproductive and respiratory syndrome virus (PRRSV) is one of the most economically important pathogens for the global pork industry, characterized for its genetic variation and unsatisfied heterological protection from vaccines. A high-throughput screening platform for developing anti-PRRSV therapies is urgently needed. Here, an 11-amino-acid subunit HiBiT derived from NanoLuc luciferase was inserted into the PRRSV genome at four loci of the Nsp2 coding region or as an additional TRS2 driven open reading frame (ORF) between the ORF7 and 3′-untranscribed region (3′-UTR), respectively, and five recombinant viruses with luciferase activity were successfully rescued. The virological characteristics of the representative virus RvJX-Nsp2325-HiBiT were investigated. In vitro, it displayed similar growth kinetics as the parental virus and keeps the luciferase activity and genetic stability after eight rounds of serial passages. The concept-proof test confirmed that RvJX-Nsp2325-HiBiT can be easily used to evaluate the efficacy of antiviral reagents by detecting the reduction of luciferase activity, showing a consistent trend with infectious titers, as well as to set a novel convenient virus neutralization assay based on the intensity of luciferase activity. Last, the viral proliferation, virulence, validity, and HiBiT stability were further investigated in pig inoculation study, showing that the luciferase activity can be directly detected in the tissue samples or indirectly from the MARC-145 cells inoculated with sera from RvJX-Nsp2325-HiBiT-inoculated pigs. Taken together, the results indicate that the HiBiT-tagged virus is a convenient and stable tool for evaluating viral propagation both in vitro and in vivo, which can provide a high-efficient platform for screening and evaluating anti-PRRSV therapies.IMPORTANCE Luciferase reporter tagged virus is crucial to viral quantification in the study of viral replication, pathogenesis and exploring antiviral reagents. It is urgently needed for PRRSV academia to construct a stable, fast, and high-throughput reporting system, which can be used both in vitro and in vivo. Here, an 11-amino-acid luciferase subunit was successfully inserted into the PRRSV genome; the feasibility, genetic stability, and efficiency for viral quantification both in vitro and in vivo were characterized; and the results demonstrated it has greatly improved the convenience and efficiency for screening the anti-PRRSV reagents. Furthermore, a novel luciferase-based virus neutralization assay was successfully set, which can eliminate the step of sample gradient dilution and greatly improve the convenience and throughput of neutralizing antibody testing. Predictably, it will greatly facilitate the screening and evaluating anti-PRRSV therapies, as well as the mechanistic study of its replication and pathogenesis in the future.

Selective ablation of 3' RNA ends and processive RTs facilitate direct cDNA sequencing of full-length host cell and viral transcripts.

Alternative splicing (AS) is necessary for viral proliferation in host cells and a critical regulatory component of viral gene expression. Conventional RNA-seq approaches provide incomplete coverage of AS due to their short read lengths and are susceptible to biases and artifacts introduced in prevailing library preparation methodologies. Moreover, viral splicing studies are often conducted separately from host cell transcriptome analysis, precluding an assessment of the viral manipulation of host splicing machinery. To address current limitations, we developed a quantitative full-length direct cDNA sequencing strategy to simultaneously profile viral and host cell transcripts. This nanopore-based approach couples processive reverse transcriptases with a novel one-step chemical ablation of 3′ RNA ends (termed CASPR), which decreases ribosomal RNA reads and enriches polyadenylated coding sequences. We extensively validate our approach using synthetic reference transcripts and show that CASPR doubles the breadth of coverage per transcript and increases detection of long transcripts (>4 kb), while being functionally equivalent to PolyA+ selection for transcript quantification. We used our approach to interrogate host cell and HIV-1 transcript dynamics during viral reactivation and identified novel putative HIV-1 host factors containing exon skipping or novel intron retentions and delineated the HIV-1 transcriptional state associated with these differentially regulated host factors.

Non-pathogenic grass carp reovirus infection leads to both apoptosis and autophagy in a grass carp cell line

A novel GCRV strain isolated from healthy grass carp was named as grass carp reovirus - HH196 (GCRV-HH196), and its infection mechanism remains unclear. In this study, the grass carp ovary cell line (GCO cells) was used to investigate the cell death involved in GCRV-HH196 infection. The results showed that DNA damage, cells volume reduction and cytoplasm shrinkage happened during GCRV-HH196 infection. The mRNA expression levels of pro-apoptotic genes were up-regulated during infection. Two initiators of apoptosis, caspase 8 and caspase 9, and the executioner of apoptosis, caspase 3, were all significantly activated in GCRV-HH196-infected cells. Flow cytometry analysis showed that the number of apoptotic cells in infected cells was significantly higher than that in control cells as the infection progress. Meanwhile, autophagy was also involved in the regulation of GCRV - HH196 infection. We observed that LC3 puncta existed in cytoplasm in GCRV-HH196-infected cells. Furthermore, the protein level of LC3-Ⅱ and Beclin-1 increased, while that of p-Akt decreased in GCRV-HH196-infected cells. These results demonstrated that GCRV-HH196 may regulate apoptosis and autophagy for the virus proliferation and spread, which set a foundation for further research on the interaction between GCRV-HH196 and host.

The substitution at residue 218 of the NS5 protein methyltransferase domain of Tembusu virus impairs viral replication and translation and may triggers RIG-I-like receptor signaling

Flavivirus RNA cap-methylation plays an important role in viral infection, proliferation, and escape from innate immunity. The methyltransferase (MTase) of the flavivirus NS5 protein catalyzes viral RNA methylation. The E218 amino acid of the NS5 protein MTase domain is one of the active sites of flavivirus methyltransferase. In flaviviruses, the E218A mutation abolished 2’-O methylation activity and significantly reduced N-7 methylation activity. Tembusu virus (TMUV, genus Flavivirus) was a pathogen that caused neurological symptoms in ducklings and decreased egg production in laying ducks. In this study, we focused on a comprehensive understanding of the effects of the E218A mutation on TMUV characteristics and the host immune response. E218A mutation reduced TMUV replication and proliferation, but did not affect viral adsorption and entry. Based on a TMUV replicon system, we found that the E218A mutation impaired viral translation. In addition, E218A mutant virus might be more readily recognized by RIG-I-like receptors to activate the corresponding antiviral immune signaling than WT virus. Together, our data suggest that the E218A mutation of TMUV MTase domain impairs viral replication and translation and may activates RIG-I-like receptor signaling, ultimately leading to a reduction in viral proliferation.

Intelligent Barrier for Face Mask and Body Temperature Detection

Corona virus is the most recently discovered causing deadly disease COVID-19. Situations in present world is getting worst because of new variants evolving day by day. It affects economically as well as socially causing great threat to human lives to peril. COVID-19 pandemic caused the entire globe to force for lockdowns in sequence to forestall proliferation of corona virus. A proper face mask and monitoring body temperature can help the authorities to notice people who are at the high risk of infection and prevents security guards getting infected. Omicron virus contamination gives rise to a great threat in the society regardless of age. According to the survey conducted, wearing mask can avert the proliferation of covid-19. Wearing mask is made mandatory everywhere especially in public places. WHO declared that high temperature is one of the symptom of variant. Here we can avoid the person without mask and having high temperature. Face mask detection is achieved using CNN technology specifically MobilenetV2 and temperature of a person is detected using MLX90614 IR temperature sensor and by making use of servo motor barrier movement can take place. Generally, gate remains open, only when having high risk of temperature and not having mask it closes and buzzer. The main goal is to prevent the society from deadly virus infection and making life easier

Study of the dynamics of in vitro infection with bovine gammaherpesvirus type 4 and apoptosis markers in susceptible cells

Bovine gammaherpesvirus type 4 (BoHV-4) shows tropism for the endometrium, in which it causes the death of epithelial and stroma cells. Despite having anti-apoptotic genes in its genome, experiments based on immortalized cell lines have shown that BoHV-4 induces cell death by apoptosis. In the present study, we evaluated BoHV-4 replication, pro-apoptotic (Bax) and anti-apoptotic (Bcl-2) mitochondrial genes expression and chromatin condensation in bovine endometrium primary culture cells (BEC) and in the Madin Darby bovine kidney (MDBK) cell line. Results showed that BoHV-4 has a preference for replication in BEC cells over the MDBK cell line, demonstrated by the high viral titer that is consistent with the tropism of the virus. In BEC cells, chromatin condensation was consistent with the values of viral kinetics at the late stage of infection, accompanied with a balance in the mRNA levels of apoptotic mitochondrial proteins. As a consequence, in those cells viral transmission would be enhanced by inhibiting apoptosis in the early stage of virus proliferation, allowing the complete production of viral progeny, and then, the induction of apoptosis in late stages would allow neighboring cells infection. In MDBK cells replication kinetics was coincident with the up-regulation of Bcl-2, which suggests that the productive infection in MDBK is associated with a lytic phase of the virus or another cell death pathway (probably autophagy mechanism) at the late stage of infection. The results agree with the study of nuclear morphology, where a constant chromatin condensation was observed over time. It is clear that the documented BoHV-4 apoptotic responses observed in the cell lines studied above are not valid in cells from primary cultures. The data presented in this study suggest that BoHV-4 could induce apoptosis in BEC cells without a leading role of the mitochondria pathway. Further studies will be necessary to characterize in detail the programmed cell death pathways involved in BoHV-4 infection in the primary cell cultures evaluated.

Antiviral RNAi Mechanisms to Arboviruses in Mosquitoes: microRNA Profile of Aedes aegypti and Culex quinquefasciatus from Grenada, West Indies

Mosquito-borne arboviruses, such as dengue virus, West Nile virus, Zika virus and yellow fever virus, impose a tremendous cost on the health of populations around the world. As a result, much effort has gone into the study of the impact of these viruses on human infections. Comparatively less effort, however, has been made to study the way these viruses interact with mosquitoes themselves. As ingested arboviruses infect their midgut and subsequently other tissue, the mosquito mounts a multifaceted innate immune response. RNA interference, the central intracellular antiviral defense mechanism in mosquitoes and other invertebrates can be induced and modulated through outside triggers (small RNAs) and treatments (transgenesis or viral-vector delivery). Accordingly, modulation of this facet of the mosquito’s immune system would thereby suggest a practical strategy for vector control. However, this requires a detailed understanding of mosquitoes’ endogenous small RNAs and their effects on the mosquito and viral proliferation. This paper provides an up-to-date overview of the mosquito’s immune system along with novel data describing miRNA profiles for Aedes aegypti and Culex quinquefasiatus in Grenada, West Indies.

NOMAD: metagenomic characterisation of the viral pathogen composition in outbreaks of non-malaria acute febrile illness cases

The clinical importance of non-malaria febrile acute illness (NM-AFI) in patients with a negative parasitological test has become apparent, with the progressive reduction in malaria transmission in endemic regions. Bacterial pathogens, for example Streptococcus pneumoniae and Haemophilus influenzae, which contribute disproportionally to febrile illness, are now preventable by vaccines. However, there are no vaccines, and little is known about viral NM-AFI prevalence, proliferation, virulence, and transmission chains between hosts. Although the predominant viral causes of NM-AFI are established, it is unclear if there are other NM-AFI associated emerging infectious viral pathogens that previously remained undetectable by conventional diagnostic strategies, for example severe acute respiratory syndrome coronavirus 2 (SARS-CoV-​2). Presumptive broad-spectrum antibiotic prescriptions to aparasitaemic patients not only drive drug resistance, but also lead to poor treatment outcomes. We hypothesized that insights on NM-AFI etiology, and consequently case management, could be improved by exploiting viral sequence diversity to identify viral pathogens present within metagenomics samples. We exploited simulated and existing infectious disease (Ebola, hepatitis C, chikungunya, and mosquito-borne arboviruses) metagenomic datasets to determine the composition of viral pathogens present, by implementing profile Hidden Markov Models derived from Swiss-Prot viral reference sequences for accurate pathogen detection and classification. Our analysis identified a combination of sequences from multiple viral etiological agents within the same disease sample. This approach provides a granular perspective of multiple viral etiological agents present within a single intra-host disease episode. It highlights prevalent viral strains that can subsequently be routinely detected using directed diagnostic tests to improve disease surveillance in endemic regions.

Functions of Viroporins in the Viral Life Cycle and Their Regulation of Host Cell Responses.

Viroporins are virally encoded transmembrane proteins that are essential for viral pathogenicity and can participate in various stages of the viral life cycle, thereby promoting viral proliferation. Viroporins have multifaceted effects on host cell biological functions, including altering cell membrane permeability, triggering inflammasome formation, inducing apoptosis and autophagy, and evading immune responses, thereby ensuring that the virus completes its life cycle. Viroporins are also virulence factors, and their complete or partial deletion often reduces virion release and reduces viral pathogenicity, highlighting the important role of these proteins in the viral life cycle. Thus, viroporins represent a common drug-protein target for inhibiting drugs and the development of antiviral therapies. This article reviews current studies on the functions of viroporins in the viral life cycle and their regulation of host cell responses, with the aim of improving the understanding of this growing family of viral proteins.