Polyomavirus Infections
Polyomavirus
BK Virus
Merkel cell polyomavirus
Carcinoma, Merkel Cell
Tumor Virus Infections
JC Virus
Antigens, Polyomavirus Transforming
Antigens, Viral, Tumor
Merkel Cells
Viral variant nucleotide sequences help expose leukocytic positioning in the JC virus pathway to the CNS. (1/581)
The human polyomavirus JCV lytically infects oligodendrocytes of immunosuppressed individuals leading to the fatal demyelinating disease termed progressive multifocal leukoencephalopathy (PML). Dementia, hemiparesis, and hemianopsia are the predominant presenting signs of PML. Asymptomatic JCV infection is common worldwide with approximately 80% of adults testing positive for JCV antibodies. In addition to the brain, JCV has been shown to infect tonsil, lymphoid, bone marrow, and kidney tissues. Viral variants, classified according to the nucleotide sequences of their regulatory regions, are being mapped in human tissues and cell types to help trace the pathway of JCV from a site of initial infection to target oligodendrocytes. In most literature, a dichotomy of the JCV regulatory region structure exists by tissue. B lymphocytes, however, have demonstrated the capacity to harbor JCV of diverse regulatory regions, which helps position their interaction with virus amid every stage of infection and implicates a lymphocytic role in latency. (+info)Polyomavirus infection of renal allograft recipients: from latent infection to manifest disease. (2/581)
Polyomavirus (PV) exceptionally causes a morphologically manifest renal allograft infection. Five such cases were encountered in this study, and were followed between 40 and 330 d during persistent PV renal allograft infection. Transplant (Tx) control groups without PV graft infection were analyzed for comparison. Tissue and urine samples were evaluated by light microscopy, immunohistochemistry, electron microscopy, and PCR. The initial diagnosis of PV infection with the BK strain was made in biopsies 9+/-2 mo (mean +/- SD) post-Tx after prior rejection episodes and rescue therapy with tacrolimus. All subsequent biopsies showed persistent PV infection. Intranuclear viral inclusion bodies in epithelial cells along the entire nephron and the transitional cell layer were histologic hallmarks of infection. Affected tubular cells were enlarged and often necrotic. In two patients, small glomerular crescents were found. In 54% of biopsies, infection was associated with pronounced inflammation, which had features of cellular rejection. All patients were excreting PV-infected cells in the urine. PV infection was associated with 40% graft loss (2 of 5) and a serum creatinine of 484+/-326 micromol/L (mean +/- SD; 11 mo post-Tx). Tx control groups showed PV-infected cells in the urine in 5%. Control subjects had fewer rejection episodes (P<0.05) and stable graft function (P = 0.01). It is concluded that a manifest renal allograft infection with PV (BK strain) can persist in heavily immunosuppressed patients with recurrent rejection episodes. PV mainly affects tubular cells and causes necrosis, a major reason for functional deterioration. A biopsy is required for diagnosis. Urine cytology can serve as an adjunct diagnostic tool. (+info)A novel animal model for hemangiomas: inhibition of hemangioma development by the angiogenesis inhibitor TNP-470. (3/581)
Hemangiomas represent the most frequent tumors of infancy. However, the pathogenesis of these tumors is still largely unknown, and current treatment of juvenile hemangiomas remains unsatisfactory. Here we present a novel animal model to study proliferating hemangiomas and to evaluate the effect of angiostatic compounds on their growth. Intraperitoneal (i.p.) infection of 4-day-old rats with murine polyomavirus resulted in the development of multiple cutaneous, intramuscular (i.m.), and cerebral hemangiomas with 100% frequency. Histological examination of the brain revealed the formation of immature lesions as soon as 4 days postinfection (p.i.). The subsequent exponential growth of the hemangiomas, both in number and size, was associated with severe hemorrhage and anemia. The cerebral, cutaneous, and i.m. lesions consisted of blood-filled cysts, histologically similar to human cavernous hemangiomas and stained positive for proliferating cell nuclear antigen, urokinase-type plasminogen activator, and vascular endothelial growth factor. Mature cerebral hemangiomas also expressed von Willebrand factor. Cerebral lesions caused death of the untreated animals within 19.2 +/- 1.1 days p.i. Remarkably fewer and smaller hemangiomas developed in animals that had been treated s.c. with the angiogenesis inhibitor TNP-470. Accordingly, TNP-470 (50 mg/kg), administered twice a week from 3 days p.i., significantly delayed tumor-associated mortality [mean day of death, 28.2 +/- 3.3 (P < 0.001)]. Even if therapy was initiated when cerebral hemangiomas were already macroscopically visible (i.e., 9 days p.i.), a significant delay in hemangioma-associated mortality was observed. Also, the IFN-inducer polyinosinic-polycytidylic acid caused a delay of 9 days (P < 0.005) in tumor-associated mortality when administered i.p. at 5 mg/kg, twice a week, starting at day 3 p.i. The model described here may be useful for investigating (a) the angiogenic mechanism(s) underlying hemangioma progression; and (b) the effect of anti-angiogenic compounds on vascular tumor growth. (+info)Discrimination between sialic acid-containing receptors and pseudoreceptors regulates polyomavirus spread in the mouse. (4/581)
Variations in the polyomavirus major capsid protein VP1 underlie important biological differences between highly pathogenic large-plaque and relatively nonpathogenic small-plaque strains. These polymorphisms constitute major determinants of virus spread in mice and also dictate previously recognized strain differences in sialyloligosaccharide binding. X-ray crystallographic studies have shown that these determinants affect binding to the sialic acids. Here we report results of further experiments designed to test the importance of specific contacts between VP1 and the carbohydrate moieties of the receptor. With minor exceptions, substitutions at positions predicted from crystallography to be important in binding the terminal alpha-2,3-linked sialic acid or the penultimate sugar (galactose) destroyed the ability of the virus to replicate in cell culture. Substitutions that prevented binding to a branched disialyloligosaccharide were found to result in viruses that were both viable in culture and tumorigenic in the mouse. Conversely, substitutions that allowed recognition and binding of the branched carbohydrate chain inhibited spread in the mouse, though the viruses remained viable in culture. Mice of five different inbred strains, all highly susceptible to large-plaque virus, showed resistance to the spread of polyomavirus strains bearing the VP1 type which binds the branched-chain receptor. We suggest that glycoproteins bearing the appropriate O-linked branched sialyloligosaccharide chains are effective pseudoreceptors in the host and that they block the spread of potentially tumorigenic or virulent virus strains. (+info)Mechanisms of cell transformation induced by polyomavirus. (5/581)
Polyomavirus is a DNA tumor virus that induces a variety of tumors in mice. Its genome encodes three proteins, namely large T (LT), middle T (MT), and small T (ST) antigens, that have been implicated in cell transformation and tumorigenesis. LT is associated with cell immortalization, whereas MT plays an essential role in cell transformation by binding to and activating several cytoplasmic proteins that participate in growth factor-induced mitogenic signal transduction to the nucleus. The use of different MT mutants has led to the identification of MT-binding proteins as well as analysis of their importance during cell transformation. Studying the molecular mechanisms of cell transformation by MT has contributed to a better understanding of cell cycle regulation and growth control. (+info)Wild-derived inbred mice have a novel basis of susceptibility to polyomavirus-induced tumors. (6/581)
Polyomavirus induces a broad array of tumors when introduced into newborn mice of certain standard inbred strains, notably those bearing the H-2(k) haplotype. Susceptibility in these mice is conferred by an endogenous mouse mammary tumor virus superantigen (Mtv-7 sag) that acts to delete T cells required for polyomavirus-induced tumor immunosurveillance. In the present study we show that mice of two wild-derived inbred strains, PERA/Ei (PE) and CZECH II/Ei (CZ), are highly susceptible to polyomavirus but carry no detectable Mtv sag-related sequences and show no evidence of Vbeta deletion. C57BR/cdJ (BR) mice, which are H-2(k) but lack the endogenous Mtv-7, are highly resistant based on an effective anti-polyomavirus tumor immune response. When crossed with BR, both PE and CZ mice transmit their susceptibility in a dominant fashion, indicating a mechanism(s) that overrides the immune response of BR. Susceptibility in PE and CZ mice is not based on interference with antigen processing or presentation since cytotoxic T cells from BR can efficiently kill F(1)-derived tumor cells in vitro. The expected precursors of polyomavirus-specific cytotoxic T cells are present in both the wild inbred animals and their F(1) progeny. These findings indicate a novel basis of susceptibility that operates independently of endogenous superantigen and prevents the development of tumor immunity. (+info)The distribution and kinetics of polyomavirus in lungs of intranasally infected newborn mice. (7/581)
The primary cell types that sustain polyomavirus (Py) replication following intranasal infection as well as the nature of the host cellular response to Py were unknown. As this is an essential and specific site for virus entry, it seems likely that viral gene function must be adapted to these mucosal tissues. Using immunohistochemistry and in situ hybridization, we determined the cell types in the lung that support Py gene expression and replication following intranasal inoculation of newborn mice within 24 h of birth. Lungs were collected daily from days 1 to 10 postinfection for Py DNA and early T antigen analysis and for histological examination by H&E staining, using methods that preserve the delicate newborn lung architecture. Viral DNA was present in increasing quantities from 2 to 6 dpi in a subset of the Clara cells lining the inner lumen of the bronchi and bronchioles, while T antigen expression was present in a majority of the cells in the bronchi and bronchiole lumen. A distinct and transient pattern of hyperplasia was observed among the cells expressing T antigen and was present from 3 through 6 dpi. Py DNA-containing cells exfoliated into the bronchiole lumen and alveolar ducts, but Py T antigen was not detected in these cells. Py DNA was first detected at 2 dpi, increased through 6 dpi, and abruptly declined through 9 dpi at which time there was no sign of viral DNA in the lungs by in situ hybridization. An unusual infiltration of neutrophils began before the presence of exfoliated cells or Py replication and continued for 2-3 days and was followed by a lymphocytic infiltration at 8-10 dpi lasting 2-3 days. Neither the hyperplasia nor the neutrophil infiltration occurred following infection with the MOP1033 MT-Ag or RB1 LT-Ag mutants of Py. In addition, both the neutrophil infiltration and the transient hyperplasia are in stark contrast to the heavy macrophage infiltration that follows infection of lungs with mouse adenovirus. Thus it appears that Py elicits a distinct host response pattern not seen with other DNA viral infections. (+info)Polyomaviruria in renal transplant patients is not correlated to the cold ischemia period or to rejection episodes. (8/581)
Polyomaviruria was observed in one-third of all renal transplant patients, irrespective of whether their renal grafts came from a living or cadaver donor, and was not correlated to graft rejection episodes. This suggests that the renal graft ischemia period is not the major cause of polyomavirus reactivation and that reactivation of polyomavirus is not a dominant cause of graft rejection. (+info)Polyomavirus infections refer to the infectious diseases caused by polyomaviruses, a type of small, non-enveloped DNA viruses that are capable of infecting humans and animals. There are several different types of polyomaviruses that can cause infection, including JC virus (JCV), BK virus (BKV), KI virus (KIV), WU virus (WUV), and Merkel cell polyomavirus (MCPyV).
Infection with these viruses typically occurs during childhood and is usually asymptomatic or associated with mild respiratory illness. However, in immunocompromised individuals, such as those with HIV/AIDS or organ transplant recipients, polyomavirus infections can lead to more serious complications, including nephropathy (BKV), progressive multifocal leukoencephalopathy (JCV), and Merkel cell carcinoma (MCPyV).
Diagnosis of polyomavirus infections typically involves the detection of viral DNA or antigens in clinical samples, such as blood, urine, or tissue biopsies. Treatment is generally supportive and aimed at managing symptoms, although antiviral therapy may be used in some cases. Prevention strategies include good hygiene practices and avoiding close contact with individuals who are known to be infected.
Polyomavirus is a type of double-stranded DNA virus that belongs to the family Polyomaviridae. These viruses are small, non-enveloped viruses with an icosahedral symmetry. They have a relatively simple structure and contain a circular genome.
Polyomaviruses are known to infect a wide range of hosts, including humans, animals, and birds. In humans, polyomaviruses can cause asymptomatic infections or lead to the development of various diseases, depending on the age and immune status of the host.
There are several types of human polyomaviruses, including:
* JC virus (JCV) and BK virus (BKV), which can cause severe disease in immunocompromised individuals, such as those with HIV/AIDS or organ transplant recipients. JCV is associated with progressive multifocal leukoencephalopathy (PML), a rare but often fatal demyelinating disease of the central nervous system, while BKV can cause nephropathy and hemorrhagic cystitis.
* Merkel cell polyomavirus (MCPyV), which is associated with Merkel cell carcinoma, a rare but aggressive form of skin cancer.
* Trichodysplasia spinulosa-associated polyomavirus (TSV), which is associated with trichodysplasia spinulosa, a rare skin disorder that affects immunocompromised individuals.
Polyomaviruses are typically transmitted through respiratory droplets or direct contact with infected bodily fluids. Once inside the host, they can establish latency in various tissues and organs, where they may remain dormant for long periods of time before reactivating under certain conditions, such as immunosuppression.
Prevention measures include good hygiene practices, such as handwashing and avoiding close contact with infected individuals. There are currently no vaccines available to prevent polyomavirus infections, although research is ongoing to develop effective vaccines against some of the more pathogenic human polyomaviruses.
BK virus, also known as BK polyomavirus, is a type of virus that belongs to the Polyomaviridae family. It is named after the initials of a patient in whom the virus was first isolated. The BK virus is a common infection in humans and is typically acquired during childhood. After the initial infection, the virus remains dormant in the body, often found in the urinary tract and kidneys.
In immunocompetent individuals, the virus usually does not cause any significant problems. However, in people with weakened immune systems, such as those who have undergone organ transplantation or have HIV/AIDS, BK virus can lead to severe complications. One of the most common manifestations of BK virus infection in immunocompromised individuals is hemorrhagic cystitis, a condition characterized by inflammation and bleeding in the bladder. In transplant recipients, BK virus can also cause nephropathy, leading to kidney damage or even failure.
There is no specific treatment for BK virus infection, but antiviral medications may be used to help control the virus's replication in some cases. Maintaining a strong immune system and monitoring viral load through regular testing are essential strategies for managing BK virus infections in immunocompromised individuals.
Merkel cell polyomavirus (MCPyV) is a type of virus from the Polyomaviridae family that is known to be associated with Merkel cell carcinoma, a rare and aggressive form of skin cancer. The virus was first identified in 2008 and is believed to play a role in the development of most cases of this cancer.
MCPyV is a small, double-stranded DNA virus that is typically acquired during childhood and remains dormant in the body. However, in some individuals, the virus can become reactivated and integrate into the host's cellular DNA, leading to the production of viral oncoproteins that can disrupt normal cell growth and division. This disruption can ultimately result in the formation of Merkel cell carcinoma.
It is important to note that while MCPyV infection is necessary for the development of Merkel cell carcinoma, it is not sufficient on its own. Other factors, such as UV radiation exposure, age, and a weakened immune system, are also believed to contribute to the development of this cancer.
Merkel cell carcinoma (MCC) is a rare and aggressive type of skin cancer that originates from the uncontrolled growth of Merkel cells, which are specialized nerve cells found in the top layer of the skin (epidermis). These cells are responsible for touch sensation. MCC typically presents as a painless, firm, rapidly growing nodule or mass, often on sun-exposed areas such as the head, neck, and arms of older adults.
The primary risk factors for Merkel cell carcinoma include:
1. Exposure to ultraviolet (UV) radiation from sunlight or tanning beds
2. Advanced age (most commonly occurs in people over 50)
3. A weakened immune system due to conditions like HIV/AIDS, organ transplantation, or long-term use of immunosuppressive medications
4. History of other types of skin cancer, such as melanoma or basal cell carcinoma
5. Fair skin and light eye color
MCC is considered an aggressive cancer because it can spread quickly to nearby lymph nodes and other parts of the body (metastasize). The major prognostic factor for MCC is the presence or absence of lymph node involvement at the time of diagnosis. Early detection and treatment are crucial for improving outcomes.
Standard treatments for Merkel cell carcinoma include surgical excision, radiation therapy, and chemotherapy. Immunotherapy with drugs like avelumab has also shown promising results in treating advanced stages of MCC. Regular follow-up care is essential to monitor for recurrence or metastasis.
A tumor virus infection is a condition in which a person's cells become cancerous or transformed due to the integration and disruption of normal cellular functions by a viral pathogen. These viruses are also known as oncoviruses, and they can cause tumors or cancer by altering the host cell's genetic material, promoting uncontrolled cell growth and division, evading immune surveillance, and inhibiting apoptosis (programmed cell death).
Examples of tumor viruses include:
1. DNA tumor viruses: These are double-stranded DNA viruses that can cause cancer in humans. Examples include human papillomavirus (HPV), hepatitis B virus (HBV), and Merkel cell polyomavirus (MCV).
2. RNA tumor viruses: Also known as retroviruses, these single-stranded RNA viruses can cause cancer in humans. Examples include human T-cell leukemia virus type 1 (HTLV-1) and human immunodeficiency virus (HIV).
Tumor virus infections are responsible for approximately 15-20% of all cancer cases worldwide, making them a significant public health concern. Prevention strategies, such as vaccination against HPV and HBV, have been shown to reduce the incidence of associated cancers.
The JC (John Cunningham) virus, also known as human polyomavirus 2 (HPyV-2), is a type of double-stranded DNA virus that belongs to the Polyomaviridae family. It is named after the initials of the patient in whom it was first identified.
JC virus is a ubiquitous virus, meaning that it is commonly found in the general population worldwide. Most people get infected with JC virus during childhood and do not experience any symptoms. After the initial infection, the virus remains dormant in the kidneys and other organs of the body.
However, in individuals with weakened immune systems, such as those with HIV/AIDS or who have undergone organ transplantation, JC virus can reactivate and cause a serious brain infection called progressive multifocal leukoencephalopathy (PML). PML is a rare but often fatal disease that affects the white matter of the brain, causing cognitive decline, weakness, and paralysis.
There is currently no cure for PML, and treatment is focused on managing the underlying immune deficiency and controlling the symptoms of the disease.
Polyomavirus transforming antigens refer to specific proteins expressed by polyomaviruses that can induce cellular transformation and lead to the development of cancer. These antigens are called large T antigen (T-Ag) and small t antigen (t-Ag). They manipulate key cellular processes, such as cell cycle regulation and DNA damage response, leading to uncontrolled cell growth and malignant transformation.
The large T antigen is a multifunctional protein that plays a crucial role in viral replication and transformation. It has several domains with different functions:
1. Origin binding domain (OBD): Binds to the viral origin of replication, initiating DNA synthesis.
2. Helicase domain: Unwinds double-stranded DNA during replication.
3. DNA binding domain: Binds to specific DNA sequences and acts as a transcriptional regulator.
4. Protein phosphatase 1 (PP1) binding domain: Recruits PP1 to promote viral DNA replication and inhibit host cell defense mechanisms.
5. p53-binding domain: Binds and inactivates the tumor suppressor protein p53, promoting cell cycle progression and preventing apoptosis.
6. Rb-binding domain: Binds to and inactivates the retinoblastoma protein (pRb), leading to deregulation of the cell cycle and uncontrolled cell growth.
The small t antigen shares a common N-terminal region with large T antigen but lacks some functional domains, such as the OBD and helicase domain. Small t antigen can also bind to and inactivate PP1 and pRb, contributing to transformation. However, its primary role is to stabilize large T antigen by preventing its proteasomal degradation.
Polyomavirus transforming antigens are associated with various human cancers, such as Merkel cell carcinoma (caused by Merkel cell polyomavirus) and some forms of brain tumors, sarcomas, and lymphomas (associated with simian virus 40).
Capsid proteins are the structural proteins that make up the capsid, which is the protective shell of a virus. The capsid encloses the viral genome and helps to protect it from degradation and detection by the host's immune system. Capsid proteins are typically arranged in a symmetrical pattern and can self-assemble into the capsid structure when exposed to the viral genome.
The specific arrangement and composition of capsid proteins vary between different types of viruses, and they play important roles in the virus's life cycle, including recognition and binding to host cells, entry into the cell, and release of the viral genome into the host cytoplasm. Capsid proteins can also serve as targets for antiviral therapies and vaccines.
Viral DNA refers to the genetic material present in viruses that consist of DNA as their core component. Deoxyribonucleic acid (DNA) is one of the two types of nucleic acids that are responsible for storing and transmitting genetic information in living organisms. Viruses are infectious agents much smaller than bacteria that can only replicate inside the cells of other organisms, called hosts.
Viral DNA can be double-stranded (dsDNA) or single-stranded (ssDNA), depending on the type of virus. Double-stranded DNA viruses have a genome made up of two complementary strands of DNA, while single-stranded DNA viruses contain only one strand of DNA.
Examples of dsDNA viruses include Adenoviruses, Herpesviruses, and Poxviruses, while ssDNA viruses include Parvoviruses and Circoviruses. Viral DNA plays a crucial role in the replication cycle of the virus, encoding for various proteins necessary for its multiplication and survival within the host cell.
Antigens are substances that trigger an immune response in the body, leading to the production of antibodies. Antigens can be proteins, polysaccharides, or other molecules found on the surface of cells or viruses.
Viral antigens are antigens that are present on the surface of viruses. When a virus infects a cell, it may display viral antigens on the surface of the infected cell. This can alert the immune system to the presence of the virus and trigger an immune response.
Tumor antigens are antigens that are present on the surface of cancer cells. These antigens may be unique to the cancer cells, or they may be similar to antigens found on normal cells. Tumor antigens can be recognized by the immune system as foreign, leading to an immune response against the cancer cells.
It is important to note that not all viral infections lead to cancer, and not all tumors are caused by viruses. However, some viruses have been linked to an increased risk of certain types of cancer. For example, human papillomavirus (HPV) has been associated with an increased risk of cervical, anal, and oral cancers. In these cases, the virus may introduce viral antigens into the cells it infects, leading to an altered presentation of tumor antigens on the surface of the infected cells. This can potentially trigger an immune response against both the viral antigens and the tumor antigens, which may help to prevent or slow the growth of the cancer.
Merkel cells, also known as Merkel-Ranvier cells or tactile epithelial cells, are specialized sensory neuroendocrine cells found in the basal layer of the epidermis, hair follicles, and mucous membranes. They are mechanoreceptors that play a crucial role in touch sensation and the initiation of the sense of touch or tactile perception. Merkel cells have neurosecretory granules and are connected to afferent nerve fibers through synaptic junctions known as Merkel discs or tactile disks. They are most abundant in areas with high tactile sensitivity, such as the fingertips, lips, and oral mucosa.
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