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2LLH , 2P1B , 2VXD

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73-758: B23 may refer to: A human nucleolar protein also known as NPM1 The 2.3L, pre-revision variant of the Volvo Redblock engine Bundesstraße 23 , federal highway in Germany B-23 , national highway in Catalonia B-23 Dragon , a 1930s bomber aircraft B-23 (Michigan county highway) DLR B23 stock , a passenger train on the Docklands Light Railway in London, UK [REDACTED] Topics referred to by

146-643: A Science article reported that China had approved CanSino 's Ebola vaccine based on an Ad5 vector. It was tested in Sierra Leone , which had high HIV prevalence , making it more likely for such problems to be detected. CanSino's CEO said "we haven't seen anything with the Ebola vaccine" and speculated that HIV susceptibility might be limited to Ad5 vaccines which produced HIV proteins. In research reported in The Lancet in May,

219-426: A decade, was shipped to basic training sites on 18 October 2011. Prevention of adenovirus, as well as other respiratory illnesses, involves frequent hand washing for more than 20 seconds, avoiding touching the eyes, face, and nose with unwashed hands, and avoiding close contact with people with symptomatic adenovirus infection. Those with symptomatic adenovirus infection are additionally advised to cough or sneeze into

292-436: A distinct structure that is protease resistant and is responsible for the oligomerization and chaperone activity of these proteins. It contains several hydrophobic residues that are highly conserved (~80%) among NPM proteins. The crystal structure of NPM1 core domain (residues 9-122) shows that this domain folds into an eight stranded β-barrel with jelly roll topology forming a wedge shaped hydrophobic core that fits snugly to form

365-454: A linear dsDNA genome and are able to replicate in the nucleus of vertebrate cells using the host's replication machinery. Entry of adenoviruses into the host cell involves two sets of interactions between the virus and the host cell. Most of the action occurs at the vertices. Entry into the host cell is initiated by the knob domain of the fiber protein binding to the cell receptor. The two currently established receptors are: CD46 for

438-423: A major effort is made to limit hepatotoxicity and prevent multiple organ failure. Adenovirus dodecahedron can qualify as a potent delivery platform for foreign antigens to human myeloid dendritic cells (MDC), and that it is efficiently presented by MDC to M1-specific CD8+ T lymphocytes. A safety issue with adenoviruses is that they can cause an immune response with a related inflammatory response as occurred in

511-428: A nucleolar phosphoprotein in rat liver cells and Novikoff hepatoma ascites cells. It was named B23 as it was the 23rd spot in the B section of the 2-D gel where spots were numbered in the order of decreasing mobility. It was named numatrin independently by another group as it was found to be tightly associated with the nuclear matrix and its expression was induced upon mitogenic signals in human B lymphocytes. At around

584-561: A number of ribosomal proteins including RPL5 (Yu et al., 2006), RPS9 (Lindström and Zhang, 2008) and RPL23 (Wanzel et al., 2008). NPM3 was shown to bind to NPM1 and negatively regulate ribosome biogenesis whereas an NPM1 binding defective mutant of NPM3 did not have any effect on ribosome biogenesis (Huang et al., 2001). Interestingly, NPM1 isoform 3 that does not have a nucleic acid binding domain also inhibits ribosome biogenesis. All these findings suggest an important role of NPM1 in ribosome biogenesis. Most cancer cells have enlarged nucleoli and

657-423: A pentamer through hydrophobic interactions between the monomeric subunits. Two pentameric complexes align in a head to head fashion to form the decameric structure. A comparison between the crystal structure of human NPM1 and that of the core domains of Xenopus NO38, Xenopus Nucleoplasmin and Drosophila Nucleoplasmin like protein (dNLP) show that both the monomeric and pentameric structures are highly similar among all

730-432: A potentially fatal disease involving vasculitis and hepatitis . Type 1 infection can also cause respiratory and eye infections. CAdV-1 also affects foxes ( Vulpes vulpes and Vulpes lagopus ) and may cause hepatitis and encephalitis. Canine adenovirus 2 (CAdV-2) is one of the potential causes of kennel cough . Core vaccines for dogs include attenuated live CAdV-2, which produces immunity to CAdV-1 and CAdV-2. CAdV-1

803-622: A role in preventing protein aggregation in the densely packed nucleolus especially during ribosome biogenesis. NPM1 shows characteristic properties of molecular chaperones such as a) preventing temperature dependent and independent aggregation of proteins, b) preserving enzyme activities during thermal denaturation of several different proteins, c) promoting the renaturation of previously denatured proteins, d) preferentially binding to denatured proteins, and exposing hydrophobic regions during interaction with other proteins. NPM1 can bind to ATP, yet, its chaperoning function does not require ATP hydrolysis or

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876-419: A vehicle to administer targeted therapy , in the form of recombinant DNA or protein. This therapy has been found especially useful in treating monogenic disease (e.g. cystic fibrosis , X-linked SCID , alpha1-antitrypsin deficiency) and cancer. In China, oncolytic adenovirus is an approved cancer treatment. Specific modifications on fiber proteins are used to target Adenovirus to certain cell types;

949-476: A wide range of illnesses , from mild respiratory infections in young children (known as the common cold ) to life-threatening multi-organ disease in people with a weakened immune system . This family contains the following genera : In humans, currently there are 88 human adenoviruses (HAdVs) in seven species (Human adenovirus A to G): Different types/serotypes are associated with different conditions: All these types are called Human mastadenovirus A–G by

1022-550: A wide range of responses, from no symptoms at all to the severe infections typical of Adenovirus serotype 14 . Bat adenovirus TJM (Bt-AdV-TJM) is a novel species of the Mastadenovirus genus isolated from Myotis and Scotophilus kuhlii in China. It is most closely related to the tree shrew and canine AdVs. Two types of canine adenoviruses are well known, type 1 and 2. Type 1 (CAdV-1) causes infectious canine hepatitis ,

1095-446: Is a protein that in humans is encoded by the NPM1 gene . In humans, the NPM1 gene is located on the long arm of chromosome 5 (5q35). The gene spans 23 kb and contains 12 exons. Three transcript variants have been described. The longest isoform (294 amino acids long), encoded by transcript variant 1, is the major and the most well studied isoform of Nucleophosmin. Transcript variant 2

1168-399: Is a direct transcriptional target of oncogenic transcription factor c-myc (Zeller et al., 2001). The ability of NPM1 to suppress apoptosis and promote DNA repair might be responsible for the survival of tumor cells where NPM1 is overexpressed. All these studies suggest that NPM1 overexpression promotes tumor development and hence could function as a proto-oncogene. NPM1 was first discovered as

1241-688: Is a distinct pool localized in the nucleoplasm in contrast to the nucleolar localization of unmodified and phosphorylated NPM1. Genome-wide profiling of AcNPM1 occupancy by ChIP-sequencing reveals that it localizes to the transcription start site of many gene promoters and is co-occupied with RNA Polymerase II. The NPM1 gene is up-regulated, mutated and chromosomally translocated in many tumor types. Chromosomal aberrations involving NPM1 were found in patients with non-Hodgkin lymphoma , acute promyelocytic leukemia , myelodysplastic syndrome , and acute myelogenous leukemia . Heterozygous mice for NPM1 are vulnerable to tumor development. In solid tumors NPM1

1314-466: Is a ribosome assembly factor or a ribosome chaperone. Other characteristic properties that suggest NPM1 role in ribosome biogenesis are nucleolar localization, ability to shuttle between the nucleus and cytoplasm, ability to bind to nucleic acid and to transport pre-ribosomal particles. NPM1 also has an intrinsic ribonuclease activity that cleaves a specific site in the ITS2 (Internal transcribed spacer 2) of

1387-425: Is also presumed to function as a histone chaperone in the nucleolus. Depletion of NPM1 or overexpression of a mutant NPM1 lacking histone chaperone activity leads to a decrease in rDNA transcription. It can also bind to linker histone H1 and promote its assembly or disassembly from chromatin. NPM1 is a molecular chaperone. It was also observed to associate with preribosomes, hence it was initially thought that NPM1

1460-502: Is different from Wikidata All article disambiguation pages All disambiguation pages NPM1 4869 18148 ENSG00000181163 ENSMUSG00000057113 P06748 Q61937 NM_001355007 NM_001355010 NM_001252260 NM_001252261 NM_008722 NP_001341936 NP_001341939 NP_001239189 NP_001239190 NP_032748 Nucleophosmin (NPM), also known as nucleolar phosphoprotein B23 or numatrin ,

1533-564: Is found to be present, it may not be the cause of any symptoms. Some immunocompromised individuals can shed the virus for weeks and show no symptoms. Most infections with adenovirus result in infections of the upper respiratory tract. Adenovirus infections often present as conjunctivitis , tonsillitis (which may look exactly like strep throat and cannot be distinguished from strep except by throat culture), an ear infection , or croup . Adenoviruses types 40 and 41 can also cause gastroenteritis . A combination of conjunctivitis and tonsillitis

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1606-431: Is frequently found overexpressed, and it is thought that NPM1 could promote tumor growth by inactivation of the tumor suppressor p53/ARF pathway; on the contrary, when expressed at low levels, NPM1 could suppress tumor growth by the inhibition of centrosome duplication. Of high importance is NPM involvement in acute myelogenous leukemia , where a mutated protein lacking a folded C-terminal domain (NPM1c+) has been found in

1679-419: Is innovative because an Ad26 based vaccine is used on the first day and an Ad5 vaccine is used on day 21. Another one is ChAd-SARS-CoV-2-S ; the vaccine reportedly prevented mice that were genetically modified to have human ACE2 (hACE2) receptors, presumably receptors that allow virus-entry into the cells, from being infected with SARS-CoV-2. Possible issues with using Adenovirus as vaccine vectors include:

1752-410: Is involved in the biogenesis of ribosomes and may assist small basic proteins in their transport to the nucleolus . Its regulation through SUMOylation (by SENP3 and SENP5 ) is another facet of the protein's regulation and cellular functions. It is located in the nucleolus , but it can be translocated to the nucleoplasm in case of serum starvation or treatment with anticancer drugs. The protein

1825-511: Is largely directed at the symptoms (such as acetaminophen for fever). The antiviral drug cidofovir has helped certain of those patients who had severe cases of illness; the number helped and to what degree, and the particular complications or symptoms it helped with, and when and where this happened, were not given in the source. A doctor may give antibiotic eyedrops for conjunctivitis, while awaiting results of bacterial cultures, and to help prevent secondary bacterial infections. Currently, there

1898-622: Is localized to the nucleolus as is reported for rat B23.1 whereas the isoform 3 (B23.2) is nucleoplasmic or cytoplasmic in localization and is expressed at relatively lower levels as compared to isoform 1 in normal rat tissues and in HeLa cells. Both isoforms 1 and 3 have been shown to stimulate the replication of adenoviral DNA complexed with viral basic proteins. NPM1 is associated with nucleolar ribonucleoprotein structures and binds single-stranded and double-stranded nucleic acids, but it binds preferentially G-quadruplex forming nucleic acids. It

1971-494: Is no adenovirus vaccine available to the general public, but a vaccine is available for the United States military for Types 4 and 7. Adenoviruses have long been a popular viral vector for gene therapy due to their ability to affect both replicating and non-replicating cells, accommodate large transgenes , and code for proteins without integrating genetic material into the host cell genome. More specifically, they are used as

2044-412: Is particularly common with adenovirus infections. Some children (especially the youngest) can develop adenovirus bronchiolitis or pneumonia , both of which can be severe. In babies, adenoviruses can also cause coughing fits that look almost exactly like whooping cough . Adenoviruses can also cause viral meningitis or encephalitis . Rarely, adenovirus can cause hemorrhagic cystitis (inflammation of

2117-462: Is produced by skipping an in-frame exon (exon 8) to produce an isoform that is 265 amino acids long. However, this isoform is not well characterized and its functions and expression pattern is not well understood. Transcript variant 3 is produced by using an alternate exon (exon 10) which results in an isoform 259 amino acids long with a different C-terminal sequence. The isoforms 1 and 3 of human NPM1 are B23.1 and B23.2 respectively in rat. The isoform 1

2190-769: Is retained even at a salt concentration of 0.5 M KCl suggesting a strong binding with the help of electrostatic interactions. However, electrostatic interactions alone are not responsible for binding to histones as is suggested by the NPM1 core crystal structure. NPM1 directly binds to core histones H2B, H3 and H4 and can bind to H2A only in the presence of the H2A-H2B dimer or the core histone octamer. It can assemble nucleosomes in vitro and can decondense sperm chromatin similar to nucleoplasmin . NPM1 histone chaperone activity has been suggested to be involved in nucleosome disassembly during transcription resulting in activation of transcription. It

2263-463: Is separated by the DNA replication process into two phases: an early and a late phase. In both phases, a primary transcript that is alternatively spliced to generate monocistronic mRNAs compatible with the host's ribosome is generated, allowing for the products to be translated . The early genes are responsible for expressing mainly non-structural, regulatory proteins . The goal of these proteins

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2336-495: Is significantly larger than other viruses in its Baltimore group , it is still a very simple virus and is heavily reliant on the host cell for survival and replication. The genes of adenoviruses can generally be divided into well-conserved sets of transcription units with six early transcription units (E1A, E1B, E2A, E2B, E3 and E4) and one late transcription unit ranging from L1-L5. In addition, adenoviruses also contain two intermediate transcription units named XI and IVa2. To increase

2409-462: Is subsequently released, which can enter the nucleus via the nuclear pore . After this the DNA associates with histone molecules already present in the nucleus, which allows it to interact with the host cell transcription machinery. Then, viral gene expression can occur, without integrating the viral genome into host cell chromosomes, and new virus particles can be generated. The adenovirus life cycle

2482-658: Is threefold: to alter the expression of host proteins that are necessary for DNA synthesis ; to activate other virus genes (such as the virus-encoded DNA polymerase ); and to avoid premature death of the infected cell by the host-immune defenses (blockage of apoptosis , blockage of interferon activity, and blockage of MHC class I translocation and expression). Some adenoviruses under specialized conditions can transform cells using their early gene products. E1A (binds Retinoblastoma tumor suppressor protein ) has been found to immortalize primary cells in vitro allowing E1B (binds p53 tumor suppressor) to assist and stably transform

2555-463: The host cell via the receptor on its surface. In 2010, the structure of the human adenovirus was solved at the atomic level, making it the largest high-resolution model ever. The virus is composed of around 1 million amino acid residues and weighs around 150 MDa . The adenovirus genome is linear, non-segmented double-stranded (ds) DNA that is between 26 and 48 k bp . This allows the virus to theoretically carry 22 to 40 genes . Although this

2628-462: The ICTV , because all are members of the genus Mastadenovirus . Adenoviruses are medium-sized (90–100 nm). The virions are composed of one linear piece of double-stranded DNA inside an icosahedral capsid . 240 hexon proteins make up the bulk of the capsid, while twelve penton bases cap the icosahedron's corners. The penton bases are associated with protruding fibers that aid in attachment to

2701-411: The family Adenoviridae ) are medium-sized (90–100 nm ), nonenveloped (without an outer lipid bilayer) viruses with an icosahedral nucleocapsid containing a double-stranded DNA genome. Their name derives from their initial isolation from human adenoids in 1953. They have a broad range of vertebrate hosts; in humans, more than 50 distinct adenoviral serotypes have been found to cause

2774-648: The 'vector' to transport the surface protein gene of SARS-CoV-2". The goal is to genetically express the spike glycoprotein of severe acute respiratory syndrome coronavirus 2 ( SARS-CoV-2 ). A replication-deficient chimpanzee adenovirus vaccine vector (ChAdOx1) is used by the Oxford–AstraZeneca COVID-19 vaccine that has been approved for use. The Janssen COVID-19 vaccine uses modified recombinant adenovirus type-26 (Ad26). Recombinant adenovirus type-5 (Ad5) are being used by Ad5-nCoV , ImmunityBio and UQ-CSL V451 . The Gam-COVID-Vac (aka Sputnik-V) product

2847-509: The NPM family proteins. The human NPM1 core domain (residues 15-118) shares a sequence identity of 80%, 51% and 29% with Xenopus NO38, Nucleoplasmin and Drosophila NLP cores respectively. All of them form the same β barrel structure with jelly roll topology. NPM1 was speculated to be a hexamer under native conditions since it was found to have a molecular weight of 230–255 kDa calculated by gel filtration chromatography and sedimentation analyses. However,

2920-435: The aberrant overexpression of NPM1 has been correlated well with the increased ribosome biogenesis in highly proliferating cells. Thus NPM1 by controlling ribosome biogenesis could control the proliferative rate of cells. NPM1 knockout mouse embryos survive upto mid-gestation (9.5dpc-12.5dpc) (Colombo et al., 2005; Grisendi et al., 2005), whereas, knockout of pescadillo, a protein involved in ribosome biogenesis, leads to death of

2993-455: The adenovirus genome can occur. A terminal protein that is covalently bound to the 5' end of the adenovirus genome acts as a primer for replication. The viral DNA polymerase then uses a strand displacement mechanism, as opposed to the conventional Okazaki fragments used in mammalian DNA replication, to replicate the genome. The late phase of the adenovirus lifecycle is focused on producing sufficient quantities of structural protein to pack all

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3066-423: The adenovirus. This co-receptor molecule is αV integrin . Binding to αV integrin results in endocytosis of the virus particle via clathrin-coated pits. Attachment to αV integrin stimulates cell signaling and thus induces actin polymerization, which facilitates clathrin-mediated endocytosis, and results in virion's entry into the host cell within an endosome . Once the virus has successfully gained entry into

3139-548: The arm or elbow instead of the hand, to avoid sharing cups and eating utensils, and to refrain from kissing others. Chlorination of swimming pools can prevent outbreaks of conjunctivitis caused by adenovirus. Diagnosis is from symptoms and history. Tests are only necessary in very serious cases. Tests include blood tests, eyes, nose or throat swabs, stool sample tests, and chest x-rays. In the laboratory, adenovirus can be identified with antigen detection, polymerase chain reaction (PCR), virus isolation and serology. Even if adenovirus

3212-469: The binding of protein VI to the endsomal membrane leading to a severe membrane curvature that ultimately disrupts the endosome. These changes, as well as the toxic nature of the pentons, destroy the endosome, resulting in the movement of the virion into the cytoplasm. With the help of cellular microtubules , the virus is transported to the nuclear pore complex, whereby the adenovirus particle disassembles. Viral DNA

3285-478: The body and water. Adenoviruses are spread primarily via respiratory droplets, however they can also be spread by fecal routes and via aerosols ( airborne transmission ). Research into the molecular mechanisms underlying adenoviral transmission provide empirical evidence in support of the hypothesis that coxsackievirus/adenovirus receptors (CARs) are needed to transport adenoviruses into certain naive/progenitor cell types. Humans infected with adenoviruses display

3358-420: The cells. Nevertheless, they are reliant upon each other to successfully transform the host cell and form tumors . E1A is mostly intrinsically disordered protein and contains CR3 domain which is critical for transcriptional activation. DNA replication separates the early and late phases. Once the early genes have liberated adequate virus proteins, replication machinery, and replication substrates, replication of

3431-550: The clinical features of hepatocellular carcinoma suggesting that NPM1 overexpression could serve as a diagnostic marker for hepatocellular carcinoma. NPM1 overexpression and hyperacetylation progresses according to the increasing grade of tumor in OSCC. NPM1 overexpression also correlates well with recurrence and progression of bladder cancer to advanced stages. NPM1 overexpression is associated with acquired oestrogen-independence in human breast cancer cells (Skaar et al., 1998). Moreover, NPM1

3504-400: The context of clonal hematopoiesis of undetermined significance harboring a DNMT3A mutation, subsequent NPM1 mutations drive progression into overt myeloproliferative neoplasm. In addition, NPM1 is overexpressed in many solid tumors including gastric, colon, breast, ovary, bladder, oral, thyroid, brain, liver, prostate cancer and multiple myeloma. NPM1 overexpression correlates well with

3577-451: The crystal structure of the NPM1 core clearly shows that it is a pentamer. The pentamer-pentamer interface consists of several water molecules involved in hydrogen bonding between the two pentamers. Moreover, ten charge based interactions between the Asp of the highly conserved AKDE loop and Lys82 give additional stability. Comparison of dNLP and Nucleoplasmin structures has revealed that formation of

3650-493: The cytoplasm in patients. This aberrant localization has been linked to the development of the disease, and is associated with improved clinical outcomes. Strategies against this subtype of acute myelogenous leukemia include the refolding of the C-terminal domain using pharmalogical chaperones and the displacement of the protein from nucleolus to nucleoplasm, which has been linked to apoptotic mechanisms. It has also been shown that in

3723-666: The death of Jesse Gelsinger in 1999. To address this risk, the genome of the viral genes have been modified to remove some viral genes. One such modification is the gutless vector that removes almost all the viral genome. Adenovirus has been used for delivery of CRISPR/Cas9 gene editing systems, but high immune reactivity to viral infection has posed challenges in use for patients. Modified ( recombinant ) adenovirus vectors, including replication incompetent types, can deliver DNA coding for specific antigens . Adenovirus have been used to produce viral vector COVID-19 vaccines . "In four candidate COVID-19 vaccines... Ad5... serves as

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3796-425: The decamer might be facilitated by histone binding. The H2A-H2B dimer may bind to the lateral surface of the NPM1 decamer. Furthermore, comparison of the crystal structures of human NPM1 and Xenopus NO38 reveals structural plasticity in the pentamer-pentamer interface. When one of the pentamers of human NPM1 and Xenopus NO38 are superimposed, there is a large rotational offset (~20°) between the other pentamers. Further,

3869-420: The direction of the rotational offsets are opposite for human NPM1 and Xenopus NO38 when compared to Xenopus Nucleoplasmin core structure. The significance of this structural plasticity is not well understood, however, it may have a significance in the chaperone function of NPM1. NPM1 has been shown to interact with Nucleophosmin has multiple binding partners: Adenoviral Adenoviruses (members of

3942-605: The embryos at morula stages (2.5 dpc) (Lerch-Gaggl et al., 2002). This suggests that either NPM1 may not be essential for ribosome biogenesis, as other proteins could have overlapping functions with NPM1 or there could be other factors such as ribosome storage in oocytes that could have compensated for the loss of NPM1 in NPM1 null embryos (Grisendi et al., 2006). NPM1 has been shown to be an important co-activator for RNA Polymerase II driven transcription. Acetylation of NPM1 enhances this activity through increased histone binding and chaperone activity. Intriguingly acetylated NPM1 (AcNPM1)

4015-451: The general population or on people with weakened immune systems. In the past, US military recruits were vaccinated against two serotypes of adenovirus, with a corresponding decrease in illnesses caused by those serotypes. That vaccine is no longer manufactured. The U.S. Army Medical Research and Materiel Command announced on 31 October 2011 that a new adenovirus vaccine, which replaces the older version that has been out of production for over

4088-417: The genetic material produced by DNA replication. Once the viral components have successfully been replicated, the virus is assembled into its protein shells and released from the cell as a result of virally induced cell lysis . Adenovirus is capable of multiplicity reactivation (MR) (Yamamoto and Shimojo, 1971). MR is the process by which two, or more, virus genomes containing lethal damage interact within

4161-432: The group B human adenovirus serotypes and the coxsackievirus/adenovirus receptor (CAR) for all other serotypes. There are some reports suggesting MHC molecules and sialic acid residues functioning in this capacity as well. This is followed by a secondary interaction, where a motif in the penton base protein (see capsomere ) interacts with an integrin molecule. It is the co-receptor interaction that stimulates entry of

4234-404: The host cell, the endosome acidifies, which alters virus topology by causing capsid components to disband. The capsid is destabilized and protein VI, which is one of the capsid constituents (see Adenovirus genome ) is released from it. Protein VI contains an N-terminal amphiphatic alpha-helix, a helical domain that exhibits both hydrophobic and hydrophilic properties. This amphipathic helix enables

4307-465: The human body develops immunity to the vector itself, making subsequent booster shots difficult or impossible. In some cases, people have pre-existing immunity to Adenoviruses, making vector delivery ineffective. The use of Ad5 vaccines for COVID-19 worried researchers who had experience with two failed trials of an Ad5 vaccine, Phambili and STEP, due to the increased risk for uncircumcised male patients of contracting HIV-1 via unprotected anal sex. At

4380-561: The infected cell to form a viable virus genome. Such MR was demonstrated for adenovirus 12 after virions were irradiated with UV light and allowed to undergo multiple infection of host cells. In a review, numerous examples of MR in different viruses were described, and it was suggested that MR is a common form of sexual interaction that provides the survival advantage of recombinational repair of genome damages. Adenoviruses are unusually stable to chemical or physical agents and adverse pH conditions, allowing for prolonged survival outside of

4453-430: The nuclear export signals (NES), nuclear localization signals (NLS) and the nucleolar localization signals (NoLS) are critical for the localization of NPM1 to the nucleolus as well as its nucleo-cytoplasmic shuttling required for its diverse array of functions. The N-terminal domain also known as the core domain (residues 1-119 of human NPM1) is the most conserved domain among the NPM family proteins. This domain folds into

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4526-426: The nucleus/nucleolus thereby promoting viral particle assembly. Further, since NPM1 can shuttle between the nucleus and the cytoplasm by virtue of its NES and NLS , it could help in co-translational folding of client proteins in the cytoplasm and promote their entry into the nucleus/nucleolus. NPM1 is a highly acidic protein and can bind to histones directly because of their basic nature. NPM1 binding to histones

4599-509: The pre-5.8S rRNA. Knockdown of NPM1 leads to changes in the profiles of ribosomes. (Grisendi et al., 2005) Degradation of NPM1 induced by ARF leads to defects in the processing of pre-ribosomal RNA from the 32S precursor rRNA to the 28S rRNA species (Itahana et al., 2003). Moreover, blocking the NPM1 nucleo-cytoplasmic shuttling inhibits ribosome subunit export resulting in a decrease in the cell growth rate showing that NPM1 exports pre-ribosomes (Maggi et al., 2008). Furthermore, NPM1 interacts with

4672-517: The presence of ATP. NPM1 is known to associate with pre-ribosomal particles and other nucleolar proteins. Since ribosomal proteins tend to be insoluble under physiological conditions, NPM1 presumably binds to ribosomal proteins in the nucleolus, prevent them from aggregation and promote their assembly into the ribosomal subunits. Similarly, certain viral proteins such as HIV-1 Rev that are insoluble under physiological conditions, bind to NPM1 which prevents their aggregation and allows their accumulation in

4745-448: The same term This disambiguation page lists articles associated with the same title formed as a letter–number combination. If an internal link led you here, you may wish to change the link to point directly to the intended article. Retrieved from " https://en.wikipedia.org/w/index.php?title=B23&oldid=1148187911 " Category : Letter–number combination disambiguation pages Hidden categories: Short description

4818-498: The same time, the Xenopus NO38 was discovered and was found to be homologous to Xenopus Nucleoplasmin and rat B23. The NPM1 protein can be divided into several domains with sequence motifs that are conserved across nucleoplasmin family and have important and distinct functions. The N-terminal core domain, the acidic stretches, basic domain and the aromatic nucleic acid domain make up the NPM1 protein. Further, sequence motifs such as

4891-755: The time, it was concluded that heightened risk of HIV reception may be observed for any Ad5-based vector vaccine. In October 2020, these researchers wrote in The Lancet : "On the basis of these findings, we are concerned that use of an Ad5 vector for immunisation against SARS-CoV-2 could similarly increase the risk of HIV-1 acquisition among men who receive the vaccine." Vaccines using other technologies would not be affected, but Sputnik V , Convidecia and ImmunityBio's hAd5 would. Two studies found that Ad5-specific CD4 T cells are more susceptible to HIV infection than CD4 T cells specific to certain other vectors, such as Cytomegalovirus and Canarypox . By comparison,

4964-778: The urinary bladder—a form of urinary tract infection —with blood in the urine). Most people recover from adenovirus infections by themselves, but people with immunodeficiency sometimes die of adenovirus infections, and—rarely—even previously healthy people can die of these infections. This may be because sometimes adenoviral infection can lead to cardiac disorders. For example, in one study, some cardiac samples of patients with dilated cardiomyopathy were positive for presence of adenovirus type 8. Adenoviruses are often transmitted by expectoration (e.g. aerosols), but they can also be transmitted by contact with an infected person, or by virus particles left on objects such as towels and faucet handles. Some people with adenovirus gastroenteritis may shed

5037-444: The viral gene economy, adenoviruses accommodate genes on both strands of its dsDNA meaning that most of its genome is utilized for coding proteins. An interesting feature of this viral genome is that it has a terminal 55 kDa protein associated with each of the 5' ends of the linear dsDNA. These are used as primers in viral replication and ensure that the ends of the virus' linear genome are adequately replicated. Adenoviruses possess

5110-432: The virus in their stools for months after getting over the symptoms. The virus can be passed through water in swimming pools that are not sufficiently chlorinated. As with many other illnesses, good handwashing practice is one way to inhibit the person-to-person transmission of adenoviruses. Heat and bleach will kill adenoviruses on objects. There are no proven antiviral drugs to treat adenoviral infections, so treatment

5183-542: Was identified as a phosphoprotein. However, later other post-translational modifications for NPM1 were identified including acetylation and SUMOylation. Nucleophosmin has multiple functions: NPM1 functions as a molecular chaperone for several proteins. Both the N-terminal hydrophobic core domain and acidic stretches are important for this activity. Furthermore, oligomerization of NPM1 has been shown to be necessary for maximum chaperone activity. NPM1 has been predicted to play

5256-1233: Was initially used in a vaccine for dogs, but corneal edema was a common complication. Squirrel adenovirus (SqAdV) is reported to cause enteritis in red squirrels in Europe, while gray squirrels seem to be resistant. SqAdV is most closely related to the adenovirus of guinea pigs (GpAdV). Adenovirus in reptiles is poorly understood, but research is currently in progress. Adenoviruses are also known to cause respiratory infections in horses , cattle , pigs , sheep , and goats . Equine adenovirus 1 can also cause fatal disease in immunocompromised Arabian foals , involving pneumonia and destruction of pancreatic and salivary gland tissue. Tupaia adenovirus (TAV) (tree shrew adenovirus 1) has been isolated from tree shrews. Otarine adenovirus 1 has been isolated from sea lions ( Zalophus californianus ). The fowl adenoviruses are associated with many disease conditions in domestic fowl like inclusion body hepatitis , hydropericardium syndrome , Egg drop syndrome , Quail bronchitis , Gizzard erosions and many respiratory conditions. They have also been isolated from wild black kites (Milvus migrans). Titi monkey adenovirus

5329-428: Was isolated from a colony of monkeys. Currently there is a vaccine for adenovirus type 4 and 7 for US military personnel only. US military personnel are the recipients of this vaccine because they may be at a higher risk of infection. The vaccine contains a live virus, which may be shed in stool and lead to transmission. The vaccine is not approved for use outside of the military, as it has not been tested in studied in

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