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HBV p22-интерактивирующий протеин C1QBP препятствует вирусному репликации, затрудняя образование нуклеокапсида и импорт ядерных материалов.

Как известно, циркулирующий вирус гепатита В (HBV) e антигена (HBeAg) подрывает иммунную систему хост-компьютера, чтобы заразиться хроническим вирусом ГБВ. Однако биологическая функция основной внутриклеточной формы HBEAg, в частности прекорового белка 22 кДа (p22) без N-терминального сигнала пептида, остается в значительной степени неясной. С помощью анализа сноса и масс-спектрометрии мы переопределили добавляющий C1q связывающий белок (C1QBP) как связующий белок с p22. Результаты работы Immunofluorescence показали, что C1QBP в основном локализован в митохондриальной матрице, а утечка C1QBP в

Совпадение в аннотации оригинала
The circulating hepatitis B virus (HBV) e antigen (HBeAg) is known to subvert the host immune system to benefit chronic HBV infection. Howev … sion led to the autolysosomal degradation of HBV core protein (HBc) and significantly reduced viral nucleocapsid formation in a p22-dependent manner. Additionally, a C1QBP mutant without the mitochondrial targeting signal (MTS) exhibited a greater inhibitory effect on HBV replication compared to the wild type (wt). Although HBc and p22 share the same CTD seque …

SARS-CoV-2 nucleocapsid protein interaction with YBX1 displays oncolytic properties through PKM mRNA destabilization.

BACKGROUND: SARS-CoV-2, a highly contagious coronavirus, is responsible for the global pandemic of COVID-19 in 2019. Currently, it remains u … al organoids and human colon carcinoma cells. In vivo and in vitro studies revealed that SARS-CoV-2 nucleocapsid (N) protein inhibits colon and kidney tumor growth and metastasis through the N-terminal (NTD) and the C-terminal domain (CTD). The molecular mechanism indicates that the N protein of SARS-CoV-2 interacts with YBX1, resulting in the recruitment of P …

AlphaFold2 Reveals Structural Patterns of Seasonal Haplotype Diversification in SARS-CoV-2 Nucleocapsid Protein Variants.

The COVID-19 pandemic saw the emergence of various Variants of Concern (VOCs) that took the world by storm, often replacing the ones that pr … sic disorder proved to be important for viral evolution, as evidenced by the targeted change to the nucleocapsid (N) protein at the sequence, structure, and biochemical levels. The linker region of the N-protein, which binds to the RNA genome and self-oligomerizes for efficient genome packaging, was greatly impacted by mutations throughout the pandemic, follow …

SARS-CoV-2 nucleocapsid protein promotes self-deacetylation by inducing HDAC6 to facilitate viral replication.

BACKGROUND: The global outbreak of COVID-19 caused by the SARS-CoV-2 has led to millions of deaths. This unanticipated emergency has prompte … served in different SARS-CoV-2-permissive cell lines following SARS-CoV-2 infection. The SARS-CoV-2 nucleocapsid protein (N protein) was identified as the primary viral factor responsible for upregulating HDAC6 expression. Downregulation of HDAC6 using shRNA or a specific inhibitor tubacin resulted in reduced viral replication suggesting proviral role of its d …

Immunized mice naturally process in silico-derived peptides from the nucleocapsid of SARS-CoV-2.

BACKGROUND: The nucleocapsid (N) protein of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is an excellent immunogen that promotes the production of high-titer antibodies. N protein-derived peptides identified using a bioinformatics approach can potentially be used to develop a new generation of vaccines or diagnostic methods for detecting SARS-CoV-2 and its variants. However, further studies must demonstrate their capacity to be naturally processed by the immune system. OBJECTIVE: We aimed to examine the in vivo processing and recognition of in silico-identified peptides using …

Longitudinal nucleocapsid antibody testing reveals undocumented SARS-CoV-2 infections in patients with lung cancer.

Patients diagnosed with lung cancer (LC) exhibit increased susceptibility to SARS-CoV-2 infection. Rodilla et al. monitor the levels of plasma anti-nucleocapsid antibodies within a cohort of fully vaccinated LC patients and reveal that the actual infection rate is nearly twice the documented rate, indicating a significant prevalence of unreported cases.

TRIM26-mediated degradation of nucleocapsid protein limits porcine reproductive and respiratory syndrome virus-2 infection.

Porcine reproductive and respiratory syndrome (PRRS), caused by PRRSV, has ranked among the most economically important veterinary infectious diseases globally. Recently, tripartite motif (TRIMs) family members have arisen as novel restriction factors in antiviral immunity. Noteworthy, TRIM26 was reported as a binding partner of IRF3, TBK1, TAB1, and NEMO, yet its role in virus infection remains controversial. Herein, we showed that TRIM26 bound N protein by the C-terminal PRY/SPRY domain. Moreover, ectopic expression of TRIM26 impaired PRRSV replication and induced degradation of N protein. T

Nucleocapsid Protein Recruitment to Replication-Transcription Complexes Plays a Crucial Role in Coronaviral Life Cycle.

Coronavirus (CoV) nucleocapsid (N) proteins are key for incorporating genomic RNA into progeny viral particles. In infected cells, N proteins are present at the replication-transcription complexes (RTCs), the sites of CoV RNA synthesis. It has been shown that N proteins are important for viral replication and that the one of mouse hepatitis virus (MHV), a commonly used model CoV, interacts with nonstructural protein 3 (nsp3), a component of the RTCs. These two aspects of the CoV life cycle, however, have not been linked. We found that the MHV N protein binds exclusively to nsp3 and not other R…

Mutational analysis of Rift Valley fever phlebovirus nucleocapsid protein indicates novel conserved, functional amino acids.

Rift Valley fever phlebovirus (RVFV; Phenuiviridae, Phlebovirus) is an important mosquito-borne pathogen of both humans and ruminants. The RVFV genome is composed of tripartite, single stranded, negative or ambisense RNAs. The small (S) segment encodes both the nucleocapsid protein (N) and the non-structural protein (NSs). The N protein is responsible for the formation of the viral ribonucleoprotein (RNP) complexes, which are essential in the virus life cycle and for the transcription and replication of the viral genome. There is currently limited knowledge surrounding the roles of the RVFV nu…

Mumps virus matrix, fusion, and nucleocapsid proteins cooperate for efficient production of virus-like particles.

Paramyxovirus particles, like other enveloped virus particles, are formed by budding from membranes of infected cells. To define mumps virus … ether with other viral proteins, with maximum production achieved upon coexpression of the viral M, nucleocapsid (NP), and fusion (F) proteins together. Electron microscopy analysis confirmed that VLPs were morphologically similar to MuV virions. The two MuV glycoproteins were not equal contributors to particle formation. The F protein was a major contributor …

Ribozyme-mediated decrease in mumps virus nucleocapsid mRNA level and progeny in infected vero cells.

The effects of endogenously expressed ribozymes directed to the mumps virus nucleocapsid (NP) mRNA were studied during viral infection. To this end, eukaryotic expression vectors encoding ribozymes or controls of passive hybridization effects were constructed and used to transfect mumps permissive Vero cells. Transcripts spanning trans-acting ribozymes of the hammerhead and hairpin types were designed to hydrolyze the first 5'GUC-3' sequence downstream from the initiation site and to hybridize to a 16 base sequence containing the putative cleavage site. Control vectors encoded mutated and cata…

Detection of measles virus nucleocapsid transcripts in circulating blood cells from patients with Paget disease.

Paget disease of bone is characterized by abnormalities in all phases of bone remodeling, but the fundamental cellular abnormality resides in the osteoclast (OCL). Osteoclasts in bone involved by Paget disease contain viral-like nuclear and cytoplasmic inclusions that react with antibodies directed against paramyxovirus nucleocapsid proteins, such as measles virus, respiratory syncytial virus, or canine distemper virus. However, the identity of the virus or the mechanisms responsible for its persistence or pathologic role in Paget disease is unclear. Furthermore, although Paget disease persist…

Demonstration of antigenic variation among rabies virus isolates by using monoclonal antibodies to nucleocapsid proteins.

Rabies virus isolates from terrestrial animals in six areas of the United States were examined with a panel of monoclonal antibodies to nucleocapsid proteins. Characteristic differences in immunofluorescence reactions permitted the formation of four antigenically distinct reaction groups from the 231 isolates tested. The geographic distribution of these groups corresponded well with separate rabies enzootic areas recognized by surveillance of sylvatic rabies in the United States. Distinctive reaction patterns were also identified for viral proteins from four infected bat species, and identical…

Direct interaction between human DDX1 and SARS-CoV-2 nucleocapsid protein is regulated by phosphorylation.

The nucleocapsid (N) protein of SARS-CoV-2 is essential for viral replication and transcription, in part through interactions with host proteins. Here, we delineate distinct mechanisms underlying N protein association with human RNA helicases DDX1 and DDX21. Co-immunoprecipitation assays in HEK293 cells modified to express N protein revealed that DDX1 binding requires the N protein serine-arginine (SR) region, as SR deletion markedly reduced interaction. Inhibition of glycogen synthase kinase-3 (GSK-3), which targets the SR region, serine-to-alanine substitutions within the SR region, and alka…

Evolution of a truncated nucleocapsid protein enhances SARS-CoV-2 fitness by suppressing antiviral responses.

Viruses face selective pressure to evade cellular antiviral responses to control the outcome of an infection. However, due to their limited genome size, viruses must adopt unique strategies to confront cellular sensors. Since its emergence in humans, SARS-CoV-2 accrued many mutations; however, the functional consequence of many such genetic changes remains unexplored. Here, we show that SARS-CoV-2 produces a truncated form of the nucleocapsid protein, called N*M210. Due to the acquisition of a viral transcription regulatory sequence (TRS) in the N gene, certain variants like Omicron produce a …

MolFoundry: A Structure-Aware Generative Framework for De Novo Design of PRRSV Nucleocapsid Candidate Binders.

MOTIVATION: despite being one of the most economically devastating swine pathogens, porcine reproductive and respiratory syndrome virus (PRRSV) currently lacks approved antiviral therapeutics. The viral nucleocapsid (N) protein, being structurally conserved and indispensable for genome packaging, presents an attractive yet underexplored target for small-molecule inhibitor design. However, contemporary generative frameworks are predominantly structure-agnostic, frequently failing to reconcile geometric complementarity with drug-likeness and synthetic accessibility. RESULTS: here, we present Mo…

Porcine hemagglutinating encephalomyelitis virus nucleocapsid protein targets RIG-I and IRF3 to evade IFN immunity.

The neurotropic betacoronavirus porcine hemagglutinating encephalomyelitis virus (PHEV) subverts early innate defenses to establish persistent neuronal infection. We show that PHEV activates RIG-I-MAVS signaling but hijacks this pathway to induce a delayed IRF7-dependent interferon (IFN-I) response (>12 h post-infection), permitting unchecked replication prior to late-phase immunity. Mechanistically, the viral nucleocapsid (N) protein directly engages RIG-I's caspase activation and recruitment domain (CARD) via its C-terminal domain (CTD), competitively blocking TRIM25-mediated K63-linked ubiq…

SARS-CoV-2 membrane protein recruits PP2A to dephosphorylate the nucleocapsid and promote virion production.

BACKGROUND: The nucleocapsid (N) protein of coronavirus harbors a conserved serine/arginine (SR)-rich motif whose phosphorylation by GSK-3 is essential for viral transcription and replication. Our previous studies in Severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1) and the JHM strain of mouse hepatitis virus revealed a phosphorylation-to-dephosphorylation transition during the viral life cycle, with newly synthesized N highly phosphorylated and virion-associated N hypophosphorylated. Here, we characterize this transition in SARS-CoV-2 and define its functional significance. METHOD…

SARS-CoV-2 nucleocapsid detection using a recombinant phage display-isolated single-chain fragment variable.

BACKGROUND: Diagnosis is an important factor in controlling disease. Single-chain fragment variables (scFvs) can be used for diagnosis; however, due to their immobilization issues, their application has been limited. Herein, we isolated a SARS-CoV-2 nucleocapsid phosphoprotein (NP)-specific scFv and propose it as a diagnostic tool in the scFv-displaying phage format to overcome the immobilization issue. METHOD: Spleen from NP-immunized BALB/c mice was isolated, total RNA was extracted, and cDNA was synthesized. An scFv library was constructed, using the splicing by overlap extension (SOE) PCR…

Obtaining HBV core protein VLPs carrying SARS-CoV-2 nucleocapsid conserved fragments as vaccine candidates.

The Hepatitis B core antigen (HBcAg) has been used as a carrier of several heterologous protein fragments based on its capacity to form virus-like particles (VLPs) and to activate innate and adaptive immune responses. In the present work, two chimeric proteins were designed as potential pancorona vaccine candidates, comprising the N- or C- terminal domain of SARS-CoV-2 nucleocapsid (N) protein fused to HBcAg. The recombinant proteins, obtained in E. coli, were named CN-1 and CND-1, respectively. The final protein preparations were able to form 10-25 nm particles, visualized by TEM. Both protei…