Lyssavirus rabies

Lyssavirus rabies, a.k.a. rabies, is an enveloped negative sense RNA virus that causes the famous foaming, fatal disease in both humans and animals. The initial transmission of the virus usually occurs when the saliva of an infected animal enters the blood stream via a skin breaking bite. From the wound of entry, the rabies virus travels quickly thru the neuromuscular junction and along the neural pathways to the central nervous system (CNS). The precise, targeted nature of the molecular mechanism of this transport from neuron to neuron is unknown, but the retrograde axonal transport of the rabies virus to the CNS is believed to be a key step of pathogenesis. On the molecular level, cell entry is believed to commence by the binding of the P protein from the rabies virus envelope to a matching receptor on the host neuron. This protein also binds key immune response signaling proteins, effectively dampening the host response. After receptor binding, rabies virus is endocytosed and low endosomal pH triggers the fusion of the viral envelope with the endosome membrane to release naked virus into the cytosol In addition, is it worth noting that death from rabies is not a result of physical damage caused by the virus, but rather a result of some deleterious functional alteration of the nervous system, as there is no apparent damage to infected neurons. One possible cause for disease and neuron death is that the rabies RNA most likely competes with host RNA, impairing neural cell function.

Neisseria meningitidis
N. meningitidis, a gram negative diplococci, is the main instigator of the rare but lethal disease acute bacterial meningitis. Infection occurs when the organism is transmitted by the exchange of infected body fluids, physically or aerosolized, and attaches to the epithelial cells of the nasopharyngeal or upper respiratory mucosa. On occasion, N. meningitidis crosses the mucosal barrier by initiating phagocytosis into the mucosal epithelial cells and subsequent exocytosis out of the other side of the barrier, eventually releasing the organism into the blood stream. From there it evades the host immune system and rides the blood stream to the brain. The key virulence factor of N. meningitidis is a unique Lipooligosaccharide (LOS) component of its outer membrane. LOS acts as an endotoxin which is responsible for fever, septic shock, and hemorrhage due to the destructions of red blood cells and aides on masking the pathogen from complement. In addition, N. meningitidis has a polysaccharide capsule that prevents phagocytosis by host macrophages and aids in evasion of the immune response. Fimbriae also mediate attachment of the bacterium to the epithelial cells of the nasopharynx.

References: http://en.wikipedia.org/wiki/Lyssavirus http://www.cdc.gov/rabies/transmission/virus.html Google images

Pathogens of the CNS

If I was a pathogen, and my goal was to invade the human body, I would head strain for the Central Nervous System (CNS). It is safe, secluded, and holds the keys to rest of the body. The Question is: how do you get in?

References: http://en.wikipedia.org/wiki/Neisseria_meningitidis http://www.brown.edu/Courses/Bio_160/Projects1999/bmenin/nmenin.html - Google images

Taenia solium
Taenia solium, commonly known as the pork tapeworm, is a human parasite that normally resides in the G.I. tract and can grow up to 50 meters long. It is a segmented worm attaches to the epithelial lining via two rows of teeth as seen in the picture to the right and below. Although the adults worm may look like a terrifying science fiction monster, they are relatively benign. Taenia solium larvae, on the other hand, are the real medical micro-monsters. Normally the worms eggs and larvae are flushed out through bowel movements, but occasionally the eggs pass through the lumen of the intestine into the surrounding tissues. In very unfortunate, immune compromised individuals, the eggs mature into larvae in muscle tissue and burrow their way into the brain. This entry mechanism into the CNS could be considered the brute force method. Once the larvae have reached the brain tissue, they forms cysts and can reside there slowly chomping on brain matter for years. An X-ray of an infected brain can be seen below on the far left.

Prions
Ryan Lee
Prions are the infectious agent that causes mad cow disease, CreutzfeldtJakob disease, and other spongiform encephalopathies. Unlike all previously addressed infectious agents such as bacteria, parasites and viruses, prions are not living organisms that contain genetic material. They are mutated proteins. Prion diseases are incurable and 100% fatal. A prion protein comes into existence within one seriously unfortunate individual by a single spontaneous mutation in the cellular protein PrPC . PrPC aberrantly mis-folds to form PrPSc, the infectious prion protein. The prion then aggregates in -sheetrich amyloid plaques that accumulate in the brain, causing encephalopathy, neurodegeneration and eventual death. Prion proteins (PrPSc) are then transmitted by consumption of infected brain matter. The proteins are absorbed through the intestinal lumen into the blood stream like other proteins and make their way to the brain, where they continue the disease cycle. Entry into the CNS is simple because the disease causing agent is a native protein with no antigenic properties.

References: http://en.wikipedia.org/wiki/Taenia_so lium http://www.stanford.edu/class/humbio 103/ParaSites2001/taeniasis/solium2.h tml - Google images

References: http://en.wikipedia.org/wiki/Prion http://www.pnas.org/content/95/2 3/13363.full - Google images