Editing Rabies (section)

==Cause==
[[File:Rabies Virus.jpg|thumb|Rendering of the rabies virus]]
[[File:Rabies Virus EM PHIL 1876.JPG|thumb|[[Transmission electron microscopy|TEM]] [[micrograph]] with numerous rabies [[virion]]s (small, dark grey, rodlike particles) and [[Negri bodies]] (the larger [[pathognomonic]] cellular inclusions of rabies infection)]]
[[File:Dr. Joseph Pawan.isolated rabies virus. Commemorative stamp.jpg|thumb|alt=postage stamp with man's head looking to the right|Commemorative stamp for Dr. [[Joseph Lennox Pawan]], who isolated the rabies virus]]
Rabies is caused by a number of [[lyssavirus]]es including the [[rabies virus]] and [[Australian bat lyssavirus]].<ref name="Au2014" /> [[Duvenhage lyssavirus]] may cause a rabies-like infection.<ref name="Thiel2009">{{cite journal | vauthors = van Thiel PP, de Bie RM, Eftimov F, Tepaske R, Zaaijer HL, van Doornum GJ, Schutten M, Osterhaus AD, Majoie CB, Aronica E, Fehlner-Gardiner C, Wandeler AI, Kager PA | display-authors = 6 | title = Fatal human rabies due to Duvenhage virus from a bat in Kenya: failure of treatment with coma-induction, ketamine, and antiviral drugs | journal = PLOS Neglected Tropical Diseases | volume = 3 | issue = 7 | pages = e428 | date = July 2009 | pmid = 19636367 | pmc = 2710506 | doi = 10.1371/journal.pntd.0000428 }}</ref>

The rabies virus is the [[type species]] of the ''[[Lyssavirus]]'' [[genus]], in the family'' [[Rhabdoviridae]]'', order ''[[Mononegavirales]]''. Lyssavirions have helical symmetry, with a length of about 180&nbsp;[[nanometre|nm]] and a cross-section of about 75&nbsp;nm.<ref name="Sherris">{{cite book | vauthors = Drew WL | chapter= Chapter 41: Rabies |editor= Ryan KJ |editor2=Ray CG | title = Sherris Medical Microbiology | edition = 4th | pages=597–600 | publisher = McGraw Hill | year = 2004 | isbn = 978-0-8385-8529-0 }}</ref> These virions are [[Viral envelope|enveloped]] and have a single-stranded [[RNA]] genome with [[negative-sense#Negative-sense|negative sense]]. The genetic information is packed as a [[ribonucleoprotein]] complex in which RNA is tightly bound by the viral nucleoprotein. The [[RNA genome]] of the virus encodes five genes whose order is highly conserved: nucleoprotein (N), phosphoprotein (P), matrix protein (M), glycoprotein (G), and the viral RNA polymerase (L).<ref name="pmid15885837">{{cite journal | vauthors = Finke S, Conzelmann KK | title = Replication strategies of rabies virus | journal = Virus Research | volume = 111 | issue = 2 | pages = 120–31 | date = August 2005 | pmid = 15885837 | doi = 10.1016/j.virusres.2005.04.004 }}</ref>

To enter cells, trimeric spikes on the exterior of the membrane of the virus interact with a specific cell receptor, the most likely one being the [[acetylcholine]] receptor. The cellular membrane pinches in a procession known as [[pinocytosis]] and allows entry of the virus into the cell by way of an [[endosome]]. The virus then uses the acidic environment, which is necessary, of that endosome and binds to its membrane simultaneously, releasing its five proteins and single-strand RNA into the cytoplasm.<ref name="CDC_Rabies_PEP" />

Once within a muscle or nerve cell, the virus undergoes replication. The L protein then transcribes five mRNA strands and a positive strand of RNA all from the original negative strand RNA using free nucleotides in the cytoplasm. These five mRNA strands are then translated into their corresponding proteins (P, L, N, G and M proteins) at free ribosomes in the cytoplasm. Some proteins require post-translative modifications. For example, the G protein travels through the rough [[endoplasmic reticulum]], where it undergoes [[further]] folding, and is then transported to the [[Golgi apparatus]], where a sugar group is added to it ([[glycosylation]]).<ref name="CDC_Rabies_PEP" />

When there are enough viral proteins, the viral polymerase will begin to synthesize new negative strands of RNA from the template of the positive-strand RNA. These negative strands will then form complexes with the N, P, L and M proteins and then travel to the inner membrane of the cell, where a G protein has embedded itself in the membrane. The G protein then coils around the N-P-L-M complex of proteins taking some of the host cell membrane with it, which will form the new outer envelope of the virus particle. The virus then buds from the cell.<ref name="CDC_Rabies_PEP" />

From the point of entry, the virus is [[neurotropic virus|neurotropic]], traveling along the neural pathways into the [[central nervous system]]. The virus usually first infects muscle cells close to the site of infection, where they are able to replicate without being 'noticed' by the host's immune system. Once enough virus has been replicated, they begin to bind to [[acetylcholine receptor]]s at the neuromuscular junction.<ref>{{cite journal | vauthors = Gluska S, Zahavi EE, Chein M, Gradus T, Bauer A, Finke S, Perlson E | title = Rabies Virus Hijacks and accelerates the p75NTR retrograde axonal transport machinery | journal = PLOS Pathogens | volume = 10 | issue = 8 | pages = e1004348 | date = August 2014 | pmid = 25165859 | pmc = 4148448 | doi = 10.1371/journal.ppat.1004348 }}</ref> The virus then travels through the nerve cell axon via [[Axonal transport#Retrograde transport|retrograde transport]], as its P protein interacts with [[dynein]], a protein present in the cytoplasm of nerve cells. Once the virus reaches the cell body it travels rapidly to the central nervous system (CNS), replicating in motor neurons and eventually reaching the brain.<ref name="Robbins" /> After the brain is infected, the virus travels centrifugally to the peripheral and autonomic nervous systems, eventually migrating to the salivary glands, where it is ready to be transmitted to the next host.<ref name="Baer1991" />{{rp|317}}
[[File:PHIL 2184.png|thumb|Two dogs with the paralytic, or dumb, form of rabies]]