Viral Infections Of Cns, Hiv(Nixon)

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Inflammation of brain

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Encephalitis

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Inflammation of spinal cord

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Myelitis

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Inflammation of leptomeninges

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Meningitis

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Hallmark is alteration in consciousness, lethargy, or coma

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Encephalitis

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T/F Viruses account for most encephalitis cases

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T

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Manifests with headache, stiff neck, photophobia, fever

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Meningitis

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Transverse myelitis: symptoms

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Stimulates acute transection of chord with rostral limb weakness, sensory level, loss of bowel and bladder.

ascending flaccid paralysis and rising sensory deficit and early bowel and bladder involvement

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Poliomyelitis-like syndrome: symptoms

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Involvement of anterior horn cells primarily, flaccid paralysis.

Muscle pain without sensory loss or bladder/bowel involvement

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Most common non-epidemic etiology of encephalitis

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Herpes Simplex Virus

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Difference between encephalitis between HSV1 and HSV2

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HSV1: more common and severe

HSV2: more benign, occasionally other neuro symptoms like Bell's palsy or transverse myelitis

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Characteristics of HSV encephalitis

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CSF RBCs common, PMNs early, lymphs late

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Dx and Tx of HSV Encephalitis

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Dx: CSF PCR. Gold standard.

Tx: IV Acyclovir while waiting on test results

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Characteristics of VZV neurological sequelae in children

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Common but many time undiagnosed.

Cerebellar ataxia in 0.1% of children with chickenpox as late as 3 weeks post rash.

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Characteristics of VZV neurological sequelae in adults

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Encephalitis in 0.1-.2% 0 severe.

More with immunocompromised.

Bells' palsy, transverse myelitis

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Characteristics of EBV neurological sequelae

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Aseptic meningitis. Other complications in small minority.

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How to dx acute EBV infection (aka mononucleosis)

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Elevated transaminases in 90%.

Atypical lymphocytosis in blood/CSF

Serum IgM/CSF IgG anti-VCA

Splenomegally

Lymphadenophathy

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Causative agent of Roseola

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Human Herpes Virus 6 (HHV6)

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Characteristics of HHV6 neurological sequelae in infants

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High fever, febrile seizures, subclinical meningoencephalitis.

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Prodromal phase of Rhabdoviridae (rabies!)

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Paresthesias and pain at bite site

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Two forms of rabies (Rhabdoviridae)

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Furious form and Dumb form

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Characteristics of Furious form of rabies

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Agitation, delirium, hydrophobia, myocarditis.

Brain is often grossly normal, unclear mech of CNS dysfunction

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Characteristics of Dumb form of rabies

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AScending flaccid paralysis, coma follows

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Dx of rabies

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Direct Fluorescence Antibody of nape skin bx

PCR of Saliva > CSF in confirming dx

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Post Exposure Prevention for Rabies in unvaccinated

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Local wound care, Rabies immune globulin, 4 doses of human diploid rabies vaccine

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Sx of Lymphocytic Choriomeningitis Virus (LCM)

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Fever, headache, occ LAD or rash that improves, then recurs in 2-4 Days with meningitis

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Mumps and Measles, Nipah and Hendra: what family

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Paramyxaviridae

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Characteristics of Enterovirus

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Small RNA viruses (picorna) spread by fecal contamination or respiratory-oral

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Most common etiology of meningitis, marked predilection for summer

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Enteroviruses (Coxsackie group B and echoviruses - 90%)

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viral illness in which ulcers and sores (lesions) form inside the mouth, and there is a sore throat and fever

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herpangina

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the sudden occurrence of lancinating chest pain or abdominal pain attacks, commonly associated with fever, malaise, and headaches.

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Pleurodynia

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Symptoms of Enterovirus meningitis

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Pleurodynia, herpangina, myopericarditis, rash helpful in making dx

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What season is Enterovirus meningitis most common ?

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Summer

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Occasional cause of sporadic and epidemic CNS disease (meningitis, encephalitis), pneumonia often present as well

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Adenovirus

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Tx for CNS disease associated with adenovirus

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Ribavarin, ganciclovir, cidofovir, IgG active in vitro

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Neurological sequelae of HIV

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Aseptic meningitis, encephalitis, MS like lesions, ascending flaccid paralysis, bell's palsy

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What helps to narrow down different Arthropod Borne/Arboviruses?

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Geographical location. Seasonality (most are in summer)

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LaCross Virus: charcteristics

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Predominant member of CA encephalitis group, occurs east of mississippi. 90% in <15 years old.

Mild meningitis to severe HSV-like illness.

50% with seizures.

Neurologic residua not uncommon but mortality <1%.

MRI, EEG may show focal cortical abnormalities.

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Eastern Equine Encephalitis: Why care so much about it?

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Although it's rare, it's a severe disease with 30% morality.

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West Nile virus: What human disease does it cause?

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Can cause flaccid paralysis, AMS, fever.

Killed 100 people >age 55 in 1999

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In What population does Japanese Encephalitis virus occur?

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Children under 10 y/o

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Lentivirus: defn

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Retroviruses with a long incubation period prior to disease onset

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Co-receptors for HIV

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CCR5 and CD4

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HIV Proteins that Bind to host cell CD4 and membrane

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gp120 and gp41

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HIV protein ______ binds to host cell CD4 inducing conformation change that exposes hidden site, results in ramming ______ into host membrane which then results in fusion of the host cell and viral lipid membranes and internalization of HIV particle.

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gp120; gp41

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T/F Other routes than the gp120/gp41 entry may exist for HIV

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T

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What are the mammalian genes whose primary role appears to be an intrinsic defense against retroviral infection?

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APOBEC3G: deaminate cytidines in nascent retroviral DNA

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What is APOBEC3G?

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A mammalian protein appearing to be an ancient defense against retroviruses. It deaminates cytidines in nascent retroviral DNA (HIV blocks this)

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What is the form of the virus that can be inserted into the host chromosome during integration?

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dsDNA with long terminal repeats (made from reverse transcriptase - originally ssRNA)

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Why is there such a high mutation rate in HIV?

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Reverse transcriptase lacks editing capability (does not correct errors it makes)

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What tool is used to determine if given patients' HIV isolates are mutated in such a way as to be resistant to anti-HIV drugs?

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RT-PCR

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What happens during HIV integration?

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Vpr (HIV protein) moves preintegration complex into nucleus.

INTEGRASE joins the LTRs on HIV genome ends to a cut it makes within the host chromosome

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Why is the HIV provirus untouchable by anti-HIV drugs?

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It now uses host cell DNA and RNA polymerases to replicate itself.

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What is integrase?

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HIV protein that modifies and joins LTRs on the HIV genome ends thus putting it in the host cell chromosome

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How does NF-&kappa;&beta; play a role in HIV?

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HIV doesn't replicate well in resting T cells.
NF-&kappa;&beta; is activated by cytokines.

This is why HIV RNA in plasma increases when another infection or vaccine transiently increases plasma cytokines.

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What is tat?

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HIV accessory proteins that allows a host cell RNA polymerase to make a full length HIV RNA without aborting prematurely.

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What is rev?

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HIV accessory protein that binds certain HIV RNAs to move them out of the nucleus so they can be translated into peptides and polypeptides or be packaged into new virions

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What does HIV protease do?

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Cleaves HIV precursor polypeptides within immature HIV just after it's budded.

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What effect do protease inhibitors have?

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The particle can enter another cell but not complete the viral life cycle because protease normally must cleave HIV polypeptides

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Which STIs increased frequency of transmission? How?

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HSV, syphilis. They increase local cnocentration of infected macrophages and T cells.

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What is happening in GALT during acute retroviral syndrome?

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Massive T cell depletion, along with gut epithelial tigh inflammation and injury. Result in microbial translocation of bacterial products into plasma

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What is sequelae of chronic immune activation in HIV?

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Accelerated immune system aging (immunosenescence) occurs. Drives T cell loss and reduced T cell function. Magnitude of this is predictive of T cell decline and progression to an AIDS defining illness.