Molluscum contagiosum virus

Last updated
Molluscum contagiosum virus
Molluscum contagiousum virus.jpg
Negatively stained transmission electron micrograph of Molluscum contagiosum virus virions
Virus classification OOjs UI icon edit-ltr.svg
(unranked): Virus
Realm: Varidnaviria
Kingdom: Bamfordvirae
Phylum: Nucleocytoviricota
Class: Pokkesviricetes
Order: Chitovirales
Family: Poxviridae
Genus: Molluscipoxvirus
Species:
Molluscum contagiosum virus

Molluscum contagiosum virus (MCV) is a species of DNA poxvirus that causes the human skin infection molluscum contagiosum. [1] Molluscum contagiosum affects about 200,000 people a year, about 1% of all diagnosed skin diseases. Diagnosis is based on the size and shape of the skin lesions and can be confirmed with a biopsy, as the virus cannot be routinely cultured. [2] Molluscum contagiosum virus is the only species in the genus Molluscipoxvirus. [3] MCV is a member of the subfamily Chordopoxvirinae of family Poxviridae . [4] Other commonly known viruses that reside in the subfamily Chordopoxvirinae are variola virus (cause of smallpox) and monkeypox virus . [3]

Contents

The poxvirus family uniquely contains both non-enveloped particles (mature virions), and enveloped particles (extracellular virions). [5] The structure of the virions is consistent with that of others in the poxvirus family: they are composed of a nucleocapsid, core envelope, lateral body, and an extracellular envelope. Like other poxviruses, MCV is a DNA virus that replicates in the cytoplasm instead of the nucleus. Because of this, the virus must bring all necessary enzymes for replication with it or encode the enzymes in its genome.

Structure

The Molluscum contagiosum virus virion is described as oval-shaped and has the dimension of approximately 320 nm × 250 nm × 200 nm. The virus has two distinct infectious particles called the mature virion (MV) and the enveloped virion (EV), which differ in that the EV contains a second outer cellular membrane. Poxviridae is the only virus family that contains both enveloped and non-enveloped infectious particles. Other structures of the EV and MV virion include the nucleocapsid, core wall, and two lateral bodies. [6] Before the virion is released into the cytosol, the lateral bodies are associated with the virion core through boding interactions. However, during virion release into the cytoplasm, the virion core wall expands and forces the lateral bodies to dissociate. The lateral bodies function to transport one or more vital virion proteins needed for genome replication or expression. [7]

Genome

The genome consists of a linear double-stranded DNA molecule that is approximately 190 kilobases in length. The genome is unique in that the two ends of the double-stranded DNA sequence are inverted repeats of each other. This inverted terminal sequence is 4.7 kilobases in length, but can vary from 0.7–12 kilobases among poxviruses. There are 182 genes that are encoded by Molluscum contagiosum virus. Over 100 of these genes are conserved in other viruses from the poxvirus family, such as Variola virus and Vaccinia virus . The inverted terminal sequence of MCV differs from the sequences of others in the poxvirus family because it contains genus-specific host response evasion genes. The genome contains 64% GC bases, and thus encodes a lesser amount of the stop codons UAA, UGA, and UAG compared to other poxviruses. Further gene analysis has shown the MCV genome contains many long and overlapping open reading frames. [8]

Replication cycle

Entry into cell

Molluscum contagiosum virus, similar to all poxviruses, produces two infectious particles: mature virions (MV) and extracellular virions (EV), with the EV differing from the MV in that they possess an extra cellular membrane. To enter the cell, the membrane of MV fuses to the plasma membrane, specifically glycosaminoglycans, of the host cell and then enters via macropinocytosis. This process is initiated by the presence of phosphatidylserine molecules exposed on the MV cellular membrane. [9] Similarly, the outer membrane of EV fuses to the plasma membrane, specifically glycosaminoglycans, of the host cell and also enters via macropinocytosis. After macropinocytosis, H+ is pumped inside the internalized vacuole containing EV and this acidification breaks down the outer membrane, exposing a MV like particle. For both MV and EV, the cellular membranes then fuse with the vacuole allowing the release of the virus core into the cytosol. [9] [10] The virion is then uncoated, exposing the DNA to commence replication.

Replication and transcription

Molluscum contagiosum virus, like other poxviruses, replicates entirely in the cytoplasm of the host cell. This is a property unique to poxviruses, as all other DNA viruses replicate in the nucleus. Therefore, because the host cell proteins for DNA replication are present inside the nucleus, this virus has to bring or encode for all of the proteins needed for replication. [11] Each virion sets up a region in the cytoplasm, called a 'viral factory' where DNA replication, transcription, and translation all occur sequentially.[ citation needed ]

There are three phases of DNA transcription. During the early phase, genes that encode for transcription factors, viral DNA and RNA polymerases, and proteins that stimulate host cell mitosis are transcribed by DNA dependent RNA polymerase that the virion carries with it. [10] The mRNA produced in the early phase is then translated by viral transcriptase that the virion also carries with it. Then during the intermediate phase, the proteins encoded for in the early phase are used to replicate the viral DNA. Additionally, more transcription factors are produced to help transcribe the late phase mRNA. During the late phase, the genes encoding for structural proteins and enzymes needed for future infection are transcribed and then translated. Gene expression is sequential from early to intermediate to late phase of transcription, and it is temporally regulated. [6]

Assembly and release

The virion cytoplasmic factories serve as the place where mature virions are assembled for future infection. Mature virions are released via cell lysis and aid in host to host transmission of the virus. Extracellular virions are made when the MV acquires a second membrane via the Golgi apparatus and then buds out of the cell. Extracellular virions aid in spreading the virus within the epithelial tissue. [6]

Tropism

Molluscum contagiosum virus only infects human epidermal cells. It is not spread throughout the body, which explains why the virus cannot be transmitted through coughing or sneezing. [12] People have attempted to grow the virus in cell culture to study its molecular properties, but have been largely unsuccessful due to it only infecting epidermal cells. [8]

However, there is evidence that it has the ability to adapt and survive in different types of cells in humans with severely compromised immune systems. Using qPCR analysis, it was determined that there was significant Molluscum contagiosum virus in the plasma of one patient who had a large t-cell deficiency. The patient was given CMX-001 antiviral agent as a treatment because of her severe molluscum contagiosum symptoms. Before administering the CMX-001 drug, Molluscum contagiosum virus DNA was found in 50% of her plasma samples, whereas DNA was found in 20% of samples after administering the drug. This is the first time molluscum contagiosum DNA was ever detected in the blood of a patient. [13]

Modulation of host cell processes

Several proteins produced mRNA in the intermediate phase of transcription modulate host cell processes to promote an ideal environment for the viral replication and transcription. Molecular analysis has shown that 77 MCV proteins may potentially interfere with host cell processes. However, only 7 MCV proteins have confirmed host cell functions. These proteins include MC007, MC054, MC066, MC132, MC148, MC159, and MC160. [8] The following list will give an overview of how these proteins modulate host cell processes.

Molluscum contagiosum

Round, hard, flesh colored bumps that are the symptom of Molluscum contagiosum virus infection. Molluscum contagiosum.jpg
Round, hard, flesh colored bumps that are the symptom of Molluscum contagiosum virus infection.

This is a viral infection of the skin that usually presents in children ages 1–10 and immunocompromised patients. [12] The main symptom of this disease is round, hard, flesh colored, painless bumps, with sunken centers that are apparent on the surface of the skin (Figure 1). The bumps are generally less than 6 millimeters in diameter and can become red and inflamed or itchy if a person rubs them. They are generally found on the face, neck, armpits, and hands. However, the bumps may also be found on the genitals of adults if the disease was spread through sexual contact. [4] [12] The virus can be spread directly from person to person through skin to skin contact or through fomites, which are inanimate objects contaminated with the virus. The most common fomites for molluscum contagiosum transmission are clothing, towels, bathing sponges, toys, and sports equipment. Additionally, the virus can spread to other skin areas of one's body through itching or rubbing the virus. It can also be spread in adults through sexual contact. The virus is not circulated throughout the body, and thus, cannot be spread by coughing or sneezing. The transmission of this virus can be prevented by washing hands, not sharing items, refraining from sexual contact and shaving, and by keeping the bumps clean and covered. [4] [12]

Generally, if one has a functioning immune system no treatment is needed and the bumps and virus will go away within 6–12 months of contraction. However, treatment is suggested if the bumps are on the genital area or if the person affected is immunocompromised. In healthy (non-immunocompromised) individuals, cryotherapy, curettage, laser therapy, oral therapy, or a topical therapy is suggested to treat the lesions. Cryotherapy involves freezing the lesions with liquid nitrogen, whereas curettage involves piercing the core and scraping the lesion with sterile equipment. Laser therapy involves destroying the lesion with a laser. It is a good idea to not try removing the lesions yourself, as the skin can become infected and the virus can spread to other parts of the body. A commonly prescribed oral medication used to treat the lesions is cimetidine and a topical therapy is Podophyllotoxin cream (0.5%). [12]

People with severely weakened immune systems and molluscum contagiosum may have bumps or lesions that are greater than 15 millimeters and look different from normal. Most typical therapies are ineffective in treating these people. The recommended treatment in this case are therapies that help boost the immune system. [12]

Related Research Articles

<span class="mw-page-title-main">DNA virus</span> Virus that has DNA as its genetic material

A DNA virus is a virus that has a genome made of deoxyribonucleic acid (DNA) that is replicated by a DNA polymerase. They can be divided between those that have two strands of DNA in their genome, called double-stranded DNA (dsDNA) viruses, and those that have one strand of DNA in their genome, called single-stranded DNA (ssDNA) viruses. dsDNA viruses primarily belong to two realms: Duplodnaviria and Varidnaviria, and ssDNA viruses are almost exclusively assigned to the realm Monodnaviria, which also includes some dsDNA viruses. Additionally, many DNA viruses are unassigned to higher taxa. Reverse transcribing viruses, which have a DNA genome that is replicated through an RNA intermediate by a reverse transcriptase, are classified into the kingdom Pararnavirae in the realm Riboviria.

<span class="mw-page-title-main">Cowpox</span> Disease of humans and animals

Cowpox is an infectious disease caused by the cowpox virus (CPXV). It presents with large blisters in the skin, a fever and swollen glands, historically typically following contact with an infected cow, though in the last several decades more often from infected cats. The hands and face are most frequently affected and the spots are generally very painful.

Cauliflower mosaic virus (CaMV) is a member of the genus Caulimovirus, one of the six genera in the family Caulimoviridae, which are pararetroviruses that infect plants. Pararetroviruses replicate through reverse transcription just like retroviruses, but the viral particles contain DNA instead of RNA.

<span class="mw-page-title-main">Viral protein</span>

The term viral protein refers to both the products of the genome of a virus and any host proteins incorporated into the viral particle. Viral proteins are grouped according to their functions, and groups of viral proteins include structural proteins, nonstructural proteins, regulatory proteins, and accessory proteins. Viruses are non-living and do not have the means to reproduce on their own, instead depending on their host cell's machinery to do this. Thus, viruses do not code for most of the proteins required for their replication and the translation of their mRNA into viral proteins, but use proteins encoded by the host cell for this purpose.

<i>Poxviridae</i> Family of viruses

Poxviridae is a family of double-stranded DNA viruses. Vertebrates and arthropods serve as natural hosts. There are currently 83 species in this family, divided among 22 genera, which are divided into two subfamilies. Diseases associated with this family include smallpox.

Metaviridae is a family of viruses which exist as Ty3-gypsy LTR retrotransposons in a eukaryotic host's genome. They are closely related to retroviruses: members of the family Metaviridae share many genomic elements with retroviruses, including length, organization, and genes themselves. This includes genes that encode reverse transcriptase, integrase, and capsid proteins. The reverse transcriptase and integrase proteins are needed for the retrotransposon activity of the virus. In some cases, virus-like particles can be formed from capsid proteins.

<span class="mw-page-title-main">Viral replication</span> Formation of biological viruses during the infection process

Viral replication is the formation of biological viruses during the infection process in the target host cells. Viruses must first get into the cell before viral replication can occur. Through the generation of abundant copies of its genome and packaging these copies, the virus continues infecting new hosts. Replication between viruses is greatly varied and depends on the type of genes involved in them. Most DNA viruses assemble in the nucleus while most RNA viruses develop solely in cytoplasm.

The genome and proteins of HIV (human immunodeficiency virus) have been the subject of extensive research since the discovery of the virus in 1983. "In the search for the causative agent, it was initially believed that the virus was a form of the Human T-cell leukemia virus (HTLV), which was known at the time to affect the human immune system and cause certain leukemias. However, researchers at the Pasteur Institute in Paris isolated a previously unknown and genetically distinct retrovirus in patients with AIDS which was later named HIV." Each virion comprises a viral envelope and associated matrix enclosing a capsid, which itself encloses two copies of the single-stranded RNA genome and several enzymes. The discovery of the virus itself occurred two years following the report of the first major cases of AIDS-associated illnesses.

<i>Herpesviridae</i> Family of DNA viruses

Herpesviridae is a large family of DNA viruses that cause infections and certain diseases in animals, including humans. The members of this family are also known as herpesviruses. The family name is derived from the Greek word ἕρπειν, referring to spreading cutaneous lesions, usually involving blisters, seen in flares of herpes simplex 1, herpes simplex 2 and herpes zoster (shingles). In 1971, the International Committee on the Taxonomy of Viruses (ICTV) established Herpesvirus as a genus with 23 viruses among four groups. As of 2020, 115 species are recognized, all but one of which are in one of the three subfamilies. Herpesviruses can cause both latent and lytic infections.

<i>Myxoma virus</i> Species of virus

Myxoma virus is a poxvirus in the genus Leporipoxvirus. The two broad geographic types of myxoma virus are Californian and South American. Californian myxoma virus is found on the West Coast of the United States, the Baja Peninsula of Mexico, and the southwest coast of Canada. South American or Brazilian myxoma virus is found in South and Central America. South American myxoma virus circulates in the jungle rabbit or tapeti, whereas Californian myxoma virus circulates in the brush rabbit. In their native hosts, the viruses cause the formation of benign cutaneous fibromas rather than systemic disease.

Avipoxvirus is a genus of viruses within the family Poxviridae. Poxviridae is the family of viruses which cause the afflicted organism to have poxes as a symptom. Poxviruses have generally large genomes, and other such examples include smallpox and monkeypox. Members of the genus Avipoxvirus infect specifically birds. Avipoxviruses are unable to complete their replication cycle in non-avian species. Although it is comparably slow-spreading, Avipoxvirus is known to cause symptoms like pustules full of pus lining the skin and diphtheria-like symptoms. These diphtheria-like symptoms might include diphtheric necrotic membranes lining the mouth and the upper respiratory tract. Like other avian viruses, it can be transmitted through vectors mechanically such as through mosquitoes. There is no evidence that this virus can infect humans.

Turkeypox virus is a virus of the family Poxviridae and the genus Avipoxvirus that causes turkeypox. It is one of the most common diseases in the wild turkey population. Turkeypox, like all avipoxviruses, is transmitted either through skin contact or by arthropods acting as mechanical vectors.

Chordopoxvirinae is a subfamily of viruses in the family Poxviridae. Vertebrates and arthropods serve as natural hosts. Currently, 52 species are placed in this subfamily, divided among 18 genera. Diseases associated with this subfamily include smallpox.

<span class="mw-page-title-main">Monkeypox virus</span> Species of double-stranded DNA virus

The monkeypox virus is a species of double-stranded DNA virus that causes mpox disease in humans and other mammals. It is a zoonotic virus belonging to the Orthopoxvirus genus, making it closely related to the variola, cowpox, and vaccinia viruses. MPV is oval, with a lipoprotein outer membrane. The genome is approximately 190 kb. Smallpox and monkeypox viruses are both orthopoxviruses, and the smallpox vaccine is effective against mpox if given within 3–5 years before the disease is contracted. Symptoms of mpox in humans include a rash that forms blisters and then crusts over, fever, and swollen lymph nodes. The virus is transmissible between animals and humans by direct contact to the lesions or bodily fluids. The virus was given the name monkeypox virus after being isolated from monkeys, but most of the carriers of this virus are smaller mammals.

Suipoxvirus is a genus of viruses in the family Poxviridae and subfamily Chordopoxvirinae. Swine serve as natural hosts. There is only one species in this genus: Swinepox virus. Diseases associated with this genus include asymptomatic skin disease.

Raccoonpox virus (RCN) is a double-stranded DNA virus and a member of the orthopoxviruses in the family Poxviridae and subfamily Chordopoxvirinae. Vertebrates are the natural host of Chordopoxvirinae subfamily viruses. More specifically, raccoons are the natural hosts of RCN. RCN was isolated in 1961 from the upper respiratory tissues of 2 raccoons in a group of 92 observably healthy raccoons trapped close to Aberdeen, Maryland.

A kinetic class, also known as a temporal class, is a grouping of genes in a viral genome that are expressed at the same time during the viral replication cycle. Five of the human DNA viral families have multiple kinetic classes: Poxviridae, Herpesviridae, Adenoviridae, Papillomaviridae, and Polyomaviridae. All of the genes in a particular kinetic class are activated by the same mechanism: either by the process of the virus entering the cell and uncoating, or by the products of an earlier kinetic class in what is known as a transcriptional cascade. Generally speaking, earlier kinetic classes code for enzymes that direct the viral replication process, and later kinetic classes code for structural proteins to be packaged into virions

<i>Red deerpox virus</i> Species of virus

Red deerpox virus (RDPV) is a species of virus in the genus Parapoxvirus. It has been reported in deer in New Zealand, and in wild ruminants in Italy.

Betaarterivirus suid 2 is a species of enveloped, positive-strand RNA viruses which infect domestic pigs. Members of the species are also known as porcine reproductive and respiratory syndrome virus 2. Member viruses are a type of the porcine reproductive and respiratory syndrome viruses (PRRSV). The two types of PRRSV are distinguished by which genomic cluster they are associated with. Type 1 is associated with a LV cluster. Type 2 is associated with a VR2332 cluster.

Lateral bodies are structures that sit on the concave sides of the viral core of a poxvirus and is surrounded by a membrane. They serve as immunomodulatory delivery packets, and membrane cloaking to spread poxviruses. They were first visualized using electron microscopy in 1956 and shortly after, it was shown that they detach from the viral core upon membrane fusion.

References

  1. ↑ Rao, K; Priya, N; Umadevi, H; Smitha, T (January 2013). "Molluscum contagiosum". Journal of Oral and Maxillofacial Pathology. 17 (1): 146–7. doi: 10.4103/0973-029X.110726 . PMC   3687174 . PMID   23798852.
  2. ↑ "Molluscum Contagiosum | Johns Hopkins Medicine Health Library". www.hopkinsmedicine.org. Retrieved 2019-03-10.
  3. 1 2 "Virus Taxonomy: 2018b Release". International Committee on Taxonomy of Viruses (ICTV). February 2019. Retrieved 14 March 2019.
  4. 1 2 3 "Molluscum contagiosum - Symptoms and causes". Mayo Clinic. Retrieved 2019-03-05.
  5. ↑ Humansandviruses (2015-03-24). "Poxviridae". humansandviruses. Retrieved 2019-03-10.
  6. 1 2 3 "Molluscipoxvirus ~ ViralZone page". viralzone.expasy.org. Retrieved 2019-03-11.
  7. ↑ Schmidt, Florian Ingo; Bleck, Christopher Karl Ernst; Reh, Lucia; Novy, Karel; Wollscheid, Bernd; Helenius, Ari; Stahlberg, Henning; Mercer, Jason (August 2013). "Vaccinia Virus Entry Is Followed by Core Activation and Proteasome-Mediated Release of the Immunomodulatory Effector VH1 from Lateral Bodies". Cell Reports. 4 (3): 464–476. doi: 10.1016/j.celrep.2013.06.028 . hdl: 20.500.11850/70158 . ISSN   2211-1247. PMID   23891003.
  8. 1 2 3 Senkevich, Tatiana G.; Koonin, Eugene V.; Bugert, Joachim J.; Darai, Gholamreza; Moss, Bernard (June 1997). "The Genome of Molluscum Contagiosum Virus: Analysis and Comparison with Other Poxviruses". Virology. 233 (1): 19–42. doi: 10.1006/viro.1997.8607 . ISSN   0042-6822. PMID   9201214.
  9. 1 2 Schmidt, Florian Ingo; Bleck, Christopher Karl Ernst; Helenius, Ari; Mercer, Jason (2011-08-31). "Vaccinia extracellular virions enter cells by macropinocytosis and acid-activated membrane rupture: Cell entry of vaccinia extracellular virions". The EMBO Journal. 30 (17): 3647–3661. doi:10.1038/emboj.2011.245. PMC   3181475 . PMID   21792173.
  10. 1 2 Burrell, Christopher J.; Howard, Colin R.; Murphy, Frederick A. (January 2017). Fenner and White's Medical Virology. Academic Press. pp. 229–236. doi:10.1016/b978-0-12-375156-0.00016-3. ISBN   9780123751560.
  11. ↑ Moss, B. (2013-09-01). "Poxvirus DNA Replication". Cold Spring Harbor Perspectives in Biology. 5 (9): a010199. doi:10.1101/cshperspect.a010199. ISSN   1943-0264. PMC   3753712 . PMID   23838441.
  12. 1 2 3 4 5 6 "Molluscum Contagiosum | Poxvirus | CDC". www.cdc.gov. 2019-01-03. Retrieved 2019-03-10.
  13. ↑ Cohen, Jeffrey I.; Davila, Wilmer; Ali, Mir A.; Turk, Siu-Ping; Cowen, Edward W.; Freeman, Alexandra F.; Wang, Kening (2012-01-19). "Detection of Molluscum Contagiosum Virus (MCV) DNA in the Plasma of an Immunocompromised Patient and Possible Reduction of MCV DNA With CMX-001". The Journal of Infectious Diseases. 205 (5): 794–797. doi:10.1093/infdis/jir853. ISSN   1537-6613. PMC   3274371 . PMID   22262788.
  14. ↑ Mohr, S.; Grandemange, S.; Massimi, P.; Darai, G.; Banks, L.; Martinou, J.-C.; Zeier, M.; Muranyi, W. (2008-08-13). "Targeting the Retinoblastoma Protein by MC007L, Gene Product of the Molluscum Contagiosum Virus: Detection of a Novel Virus-Cell Interaction by a Member of the Poxviruses". Journal of Virology. 82 (21): 10625–10633. doi:10.1128/jvi.01187-08. ISSN   0022-538X. PMC   2573180 . PMID   18701596.
  15. ↑ Xiang, Y.; Moss, B. (2003-02-15). "Molluscum Contagiosum Virus Interleukin-18 (IL-18) Binding Protein Is Secreted as a Full-Length Form That Binds Cell Surface Glycosaminoglycans through the C-Terminal Tail and a Furin-Cleaved Form with Only the IL-18 Binding Domain". Journal of Virology. 77 (4): 2623–2630. doi:10.1128/jvi.77.4.2623-2630.2003. ISSN   0022-538X. PMC   141116 . PMID   12552001.
  16. ↑ Shisler, J. L. (1998-01-02). "Ultraviolet-Induced Cell Death Blocked by a Selenoprotein from a Human Dermatotropic Poxvirus". Science. 279 (5347): 102–105. Bibcode:1998Sci...279..102S. doi:10.1126/science.279.5347.102. ISSN   0036-8075. PMID   9417017.
  17. ↑ Brady, Gareth; Haas, Darya A.; Farrell, Paul J.; Pichlmair, Andreas; Bowie, Andrew G. (2015-06-03). "Poxvirus Protein MC132 from Molluscum Contagiosum Virus Inhibits NF-κB Activation by Targeting p65 for Degradation". Journal of Virology. 89 (16): 8406–8415. doi:10.1128/jvi.00799-15. ISSN   0022-538X. PMC   4524246 . PMID   26041281.
  18. ↑ Jin, Qingwen; Altenburg, Jeffrey D.; Hossain, Mohammad M.; Alkhatib, Ghalib (September 2011). "Role for the conserved N-terminal cysteines in the anti-chemokine activities by the chemokine-like protein MC148R1 encoded by Molluscum contagiosum virus". Virology. 417 (2): 449–456. doi:10.1016/j.virol.2011.07.001. ISSN   0042-6822. PMC   3760151 . PMID   21802105.
  19. ↑ Randall, C. M. H.; Jokela, J. A.; Shisler, J. L. (2012-02-01). "The MC159 Protein from the Molluscum Contagiosum Poxvirus Inhibits NF- B Activation by Interacting with the I B Kinase Complex". The Journal of Immunology. 188 (5): 2371–2379. doi:10.4049/jimmunol.1100136. ISSN   0022-1767. PMC   3288875 . PMID   22301546.
  20. ↑ Nichols, D. B.; Shisler, J. L. (2009-01-21). "Poxvirus MC160 Protein Utilizes Multiple Mechanisms To Inhibit NF- B Activation Mediated via Components of the Tumor Necrosis Factor Receptor 1 Signal Transduction Pathway". Journal of Virology. 83 (7): 3162–3174. doi:10.1128/jvi.02009-08. ISSN   0022-538X. PMC   2655573 . PMID   19158250.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.