WBR0088

Author	[[PageAuthor::Ogheneochuko Ajari, MB.BS, MS [1] (Reviewed by Will Gibson, Jad Al Danaf, Rim Halaby, M.D. [2])]]
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Microbiology
Sub Category	SubCategory::Neurology, SubCategory::Infectious Disease
Prompt	[[Prompt::A 38-year old male is brought to the emergency department by his mother with complaints of hydrophobia and disorientation. She reports that he has had three episodes of seizures in the past 2 weeks. Three days later, the patient experiences vivid visual hallucinations, lapses into a coma and dies. The most likely causal organism binds to which of the following cell surface molecules?]]
Answer A	AnswerA::SNARE proteins
Answer A Explanation	[[AnswerAExp::SNARE proteins are responsible for neurotransmitter release at synaptic junctions. Clostridium tetani and clostridium botulinum produce toxins that cleave SNARE proteins and thereby cause paralysis.]]
Answer B	AnswerB::CD4 receptors
Answer B Explanation	[[AnswerBExp::HIV-1 binds to CD4 through its viral envelope protein gp120 to gain entry into host T-cells. The number of CD4-positive T cells in the blood is a marker of disease progression in HIV infected patients.]]
Answer C	AnswerC::LDL receptors
Answer C Explanation	[[AnswerCExp::LDL receptor mutations cause familial hypercholesterolemia, an autosomal dominant lipid disorder. Familial hypercholesterolemia is associated with accelerated atherosclerosis, tendon (Achilles) xanthomas and corneal arcus.]]
Answer D	AnswerD::CCR5 receptors
Answer D Explanation	[[AnswerDExp::CCR5 receptor is a co-receptor for HIV found on macrophages and Th cells. Individuals with CCR5 mutations are protected from HIV infection.]]
Answer E	AnswerE::Acetylcholine receptors
Answer E Explanation	[[AnswerEExp::The rabies virus binds to nicotinic acetylcholine receptors to travel from peripheral nerves to the brain.]]
Right Answer	RightAnswer::E
Explanation	[[Explanation::The patient in this vignette has rabies encephalitis, a viral infection that is transmitted from dog, bat, raccoon and skunk bites. The disease progresses from fever, malaise to agitation, photophobia, hydrophobia, seizures, hallucination and then to paralysis, coma and death. After the bite from an infected animal, the virus infiltrates peripheral nerves by binding to nicotinic acetylcholine receptors at the site of inoculation. The virus moves by retrograde axoplasmic transport to dorsal root ganglia and the spinal cord. The brain becomes rapidly infected when the virus gets to the spinal cord. The incubation period during which patients do not display symptoms is typically months. However, death usually occurs within days of symptom onset. On autopsy, the brains of patients will display negri bodies (pictured below), hallmark cytoplasmic inclusions found in neurons infected with the virus. Treatment for suspected rabies infection consists of wound debridement, prophylactic vaccination (active immunity) and anti-rabies IgG (passive immunity). Rabies virus is a rhabdovirus, consisting of single-stranded negative sense RNA with helical capsid symmetry. It is famous for its bullet-shaped appearance. Educational Objective: The rabies virus binds to nicotinic acetylcholine receptors to travel from peripheral nerves to the brain. As the disease progresses, more specific symptoms appear and may include insomnia, anxiety, confusion, slight or partial paralysis, excitation, hallucinations, agitation, hypersalivation (increase in saliva), difficulty swallowing, and hydrophobia (fear of water). Death usually occurs within days of the onset of these symptoms. References: First Aid 2014 page 165, Lentz TL. Rabies virus binding to an acetylcholine receptor alpha-subunit peptide. J Mol Recognit. 1990;3(2):82-8.]]
Approved	Approved::Yes
Keyword	WBRKeyword::Rabies, WBRKeyword::Virus, WBRKeyword::Viruses, WBRKeyword::Microbiology, WBRKeyword::Neurodegenerative, WBRKeyword::Hallucination, WBRKeyword::Seizure
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