Viro Lecture 3 + 4 Flashcards
Retroviridae (4)
- diploid, + ssRNA, RT for replication
- Lentivirus group = HIV (non-segmented)
- oncovirus group = blood cell cancers -> human/adult T cell leukemia (HTLV)
- outer envelope (from PM of host), w/copies of 1 envelop prot in bilayer + internal capsid (prot w/2 RNAs + RT)
HIV virion (5)
- enveloped conical capsid (type D)
- 2 + ssRNA copies and 1 RT (RNA dependent DNA pol)
- integrase (integrating virus DNA w/host)
- protease (process prots for envelope/capsid)
- 2 prots for cell attachment = gp41 + gp120 (after infection Abs released against this prot)
Clinical Syndromes of HIV (5)
- AIDS, opportunistic infections, cancers, CNS dysfunction
- all at T cells of 400/ml
- initial symptoms = mono/flu, aseptic meningitis/rash, weight lost/wasting/fatigue
- organ/system specific but all organs can be affected
- full blow AIDS when CD4 T cells <200/ml
Viral opportunistic infections (3)
- HSV 1+2, VZV (chicken pox, shingles), EBV (eyes), CMV (CNS + retinitis), HHV 8 (kaposi carcinoma) -> all at TH cells < 50ml
- HPV (warts, anal condylomata)
- HIV oral ulcers
Bacterial opportunistic infections (3)
- Tb + other mycobacteria
- TH cells < 400ml
- other bacteria, normal flora bactera
Fungal/yeast opportunistic infections (3)
- pneumocystis jirovecii pneumonia (LUNGS) -> TH cells < 200ml
- oral candidiasis w/candida albicans (thrush) -> T cells btwn 250-500 ml
- cryptocoocus neoformans = cryptococcal meningitis (meningitis + encephalitis in AIDS pts)
Protozoan opportunistic infections (1)
toxoplasma gondii = toxoplasmosis
HIV antiviral therapy (7)
- inhibit steps of replication
- Attachment/entering cell = fusion inhibitors
- RT inhibitors
- integration + txn = integrase inhibitors
- tln (prod viral prots - use monoclonal Abs) + viral protease (cleaving viral prots) = protease inhibitors
- assembly + budding inhibitors
- HAART = highly active anti-retroviral therapy
RT inhibitors (6)
- nucleoside analogs = AZT
- non-nucleoside analogs = delavirdine, nevirapine
- ddl
- 3TC = lamivudine - thiacytidine
- d4T = thymidine
- ddC = cytidine
Protease Inhibitors (1)
Ritonavir w/ idinavir and neflinavir
Togaviridae (5)
- alpha virus group - Western/Eastern/Venezuelan Equine Encephalitis virus
- Mosquito borne diseases, Wild birds are reservoirs
- Viremia, CNS infection = Encephalitis (highly linked w/horses -> fatality rates of 30-70%), arthralgia + mild fever
- Worldwide -> in spring ideal conditions for viral replication, vector pops large
- Vaccines developed against encephalitic diseases
Rubella (4)
- togaviridae, trans via respiratory droplets, crosses placenta
- teratogenic = abnormal prenatal development, problems in first trimester of gestation
- Congenital Rubella Syndrome
- Attenuated vaccine = single strain, part of MMR
- have PDA (patent ductus arteriosus) - neonate’s ductus arteriosus doesn’t close after bith
Negative Sense RNA viruses (5)
- enveloped, virion assoc enzymes, replicated in cytoplasm (orthomyxovirus replicated in nuc)
- linear non-segmented ssRNA
- Linear ssRNA w/8 segments
- Linear -> Circular ssRNA w/3 ambisense segments
- Circular ssRNA w/2 segments
linear non-segmented - ssRNA (3)
- Paramyxovirus (Mumps, Measles, RSV, Parainfluenza)
- Rhabdovirus (Rabies & VSV)
- Filovirus (Ebola & Marburg)
Linear - ssRNA w/8 segments (1)
all in same virion = Orthomyxovirus (Influenza), replicates in nuc
Linear -> Circular - ssRNA (1)
w/3 ambisense segments = Bunyavirus (California encephalitis, Hantavirus & La Cross)
Circular - ssRNA (2)
- w/2 segments: 1 neg sense & 1 ambisense (like neg-sense, but translate genes from positive strand)
- Arenavirus (Lassa fever & LCMV)
Parainfluenza (2)
- Paramyxoviridae (neg ssRNA, enveloped, helical nucleocaspid)
- single helical nucleocaspid glycoprot, croup (laryngotracheobronchitis), common cold bronchitis
Respiratory Syncytial Virus (RSV) (3)
- Paramyxoviridae (neg ssRNA, enveloped, helical nucleocaspid)
- major cause of bronchiolitis and pneumonia in babies
- Tx: Ribavirin(GMP analog) inhibits nucleoside synth + mRNA capping, inc detrimental mutations in large #
Measles (5)
- Paramyxoviridae (neg ssRNA, enveloped, helical nucleocaspid)
- fusion prot, photophobia, 3 Cs: Cough, Coryza (stuffy nose) and Conjunctivitis
- Koplik spots (grains of salt) on oral mucosa -> maculopapular rash behind ears down = giant cell pneumonia
- Rare but serious complication - subacute sclerosing panencephalitis (chronic CNS degenerative disease)
- Live vaccine: single strain = MMR
Mumps (2)
- Paramyxoviridae (neg ssRNA, enveloped, helical nucleocaspid)
- fusion prot, parotiditis (inflammation of parotid gland near ear), pancreatitis, orchitis (males, sterility), meningoencephalitis -> live vaccine = MMR
Rhabidoviridae (5)
- Rabies from dogs, raccoons, fox, bats - bullet shaped, asymptomatic, prodrome (flu symptoms, anorexia)
- Neurological symptoms (hydrophobia, dementia -> virus along nerve fibers), coma + death
- Tx: if symptoms evident -> too late, no treatment
- Must treat immediately after bite (post-exposure prophylaxis) w/HRIG or w/killed virus vaccine
- Prevention = vaccination to high risk groups/animals, pre-exposure prophylaxis, kill rabid animals
Filoviridae (3)
- filamentous, enveloped, neg RNA -> Severe hemorrhagic fever, often fatal
- Ebola, Marburg
- Ebola trans via direct contact or body fluids
Bunyaviridae (4)
- segmented neg ssRNA - enveloped helical capsid
- California encephalitis + LaCrosse encephalitis (mosquito borne, <15 years have severe case)
- Hantavirus (rodent feces - mouse shit) pulmonary syndrome - cough, myalgia, dyspnea, tachycardia, pulmonary edema and effusion + hypotension (50% mortality)
- High in UT, AZ, NM, CO
Orthomyxoviridae (3)
- neg ssRNA, enveloped, 8 segments
- Influenzavirus type A = Infect people + animals
- Influenzavirus type B & type C = Infect people, Type C viruses = mild upper respiratory disease
Influenza A + B (4)
- Enveloped
- Hemagglutinin (HA) = Entry of virus into cells, binds sialic acid (N-acetylneuraminic acid) on host cell surface
- Neuraminidase (NA) = invasive enzyme, cleaves term sialic acid, help access epi cells by liquefying mucus in resp tract
- NA inhibitors block function of NA = Anti-flu drug target
Antigenic Drift (2)
- random mutations in viral genes seen by immune sys - can change viral Ags, help evade immune sys
- Flu A + B antigenic drift responsible for epidemics (H1N2 -> H2N2) -> why people need flu vaccine every year
Antigenic shift (4)
- abrupt major change in viral antigenicity from gene recomb
- Influenza A antigenic shift assoc w/pandemics (1918 pandemic) -> H3N2 + H5N1 = H5N2
- 2 diff strains of segmented RNA virus infect same cell
- Avian (highly pathogenic) + Human flu strain infect same cell = Major new genetic combs made via gene shuffling = New highly pathogenic human flu strain
Influenza Pathenogenesis (4)
- resp droplets -> mucous mem lining resp tract, infects ciliated columnar epi cells
- HA binds to sialic acid receptors = virus phagocytosis
- M2 prot = ion channel in virus envelope, endosome pH drops to 5.5 due to nucleocapsid release into cytoplasm
- Virus interferes w/respiratory tract “clearing” mechanisms
Influenza disease (4)
- Abrupt fever, Headache, Myalgia, Sore throat, Non-productive cough
- Resp symptoms predominate - Pharyngitis, laryngitis, and tracheobronchitis -> infection confined to resp tract
- Cough + malaise 2 weeks after other symptoms disappeared
- Influenza complications = Primary viral pneumonia + Secondary bacterial pneumonia
Amantadine + Rimantadine (4)
- specific against flu type A = block M2 ion channel
- Given as prophylaxis to prevent infection, recommended for high risk people (e.g. immunosuppressed pts)
- Given therapeutically to reduce severity (ideal in first 48 hours)
- Teratogenic -> Cause fetus malformation (don’t use in preggo women)
Neuraminadase inhibitors (4)
- inhibit NA of both influenza A + B
- dec rate of infection by preventing further infection of cells = Less severe disease, Shorter duration of symptoms
- Analogs of sialic acid (SA) bind NA, block its active site => SA remain uncleaved
- on viral cell envelopes HA binds cells SA = aggregation of virus on cell surface, less virus particles released into circulation
Tamilfu (2)
- Tamiflu (Oseltamivir) = NA inhibitor, tx & prevention
- Given orally to treat uncomplicated infection in the first 48 hours of symptoms (patient over 1 year)
Zanamivir (2)
- Zanamivir (Relenza) = NA inhibitor, tx & prophylaxis
- Given by inhalation to treat infection in the first 48 hours of symptoms (patient over 5 years)
dsRNA viruses (3)
- Reoviridae = linear dsRNA, segmented, Icosahedral, double shelled, unenveloped, Virion has assoc polymerase
- Reoviruses = URT infections
- Rotaviruses = GI tract infection, major cause of infant mortality in developing countries (600,000 under 5 yearly) -> Prolonged diarrhea
Prions (3)
- transmissible particles w/o nucleic acid, only modified prot (PrPsc) -> no recombinant infection material
- No characterization of infectious particle, specific activity of purified agent extremely low
- Infection w/o protease resistant PrPsc found
Kuru (2)
- prion disease
- Subacute spongiform encephalopathy (SSE), Fore Tribe, New Guinea, Cannibalism, Human
Creutzfeldt-Jakob (2)
- prion disease
- SSE, Genetic predisposition, Ingestion of infected cow brains, Human
Fatal familial insomnia (FII) (2)
- prion disease
- human, infects part of brain -> spongiform = can’t sleep -> ppl die from this
Bovine spongiform encephalitis (BSE) (3)
- prion disease
- in cattle = mad cow disease
- in Humans = no motor control, dementia, paralysis wasting, death, non-inflammatory lesions: vacuoles + amyloid prot deposits + astrogliosis
Scrapie (2)
- prion disease
- SSE, scraping wool off on fences, sheep
Lentiviruses (5)
- HIV part of lentiviruses (lentiviruses in monkeys = simian virus = SIV)
- HIV descendant of SIV (certain SIV like HIV-1 and -2)
- HIV-2 like SIV in sooty mangabey (SIVsm) = green monkey (west Africa)
- SIVcpz (chimps) used to be closest to HIV-1 (more virulent strain)
- Zoonosis - humans contracted HIV by eating infected chimps
HIV in america (5)
- Can now see HIV presence + subtype in blood samples -> get deeper look into origin + evolution of HIV in humans
- To find source of AIDS, look for origin of HIV
- AIDS deaths/diagnoses dec, but HIV infection inc
- Inc in younger ppl, low socioeconomic status, IVDU, women
- Condoms don’t protect against Hep A, Hep B much easier to get than HIV - but vaccines for A and B
HIV transmission (3)
- Injected body fluid - blood, semen, vaginal secretions + breast milk
- Entry into body - mucous membrane (anal, oral, vaginal sex), blood-blood (needle, broken skin), perinatal (in utero, during birth, breast feeding)
- no transmission by contact
Oral Sex Transmission (4)
- not often assoc, only 5-10% of cases
- Receptive partner (person w/mouth to genital contact) at greatest risk
- Jizz in mouth, poor oral hygiene, brushing/flossing prior to sex assoc w/transmission
- Protective factor of enzymes in saliva
Perinatal transmission (3)
- dec from antiretroviral therapy in pregnancy (24% down to 8% vertical transmission w/AZT)
- Nevirapine also successful
- Women w/higher viral loads more likely to transmit than women w/low viral loads
Factors affecting transmission (2)
- STD co-infection = more likely to become infected, transmit infection
- Viral load = stage of infection, treatments
Primary Infection (3)
- 2-6 weeks average, 75-90% have symptoms
- Only way to know for sure = HIV Ab test -> waiting time = time to develop Abs
- Disease progression = infection -> primary infection/Ab development -> asymptomatic period -> AIDS (opportunistic infections, CD < 200)
Congenital Rubella Syndrome (6)
= rash at birth, low birth weight, small head size, heart abnormalities, visual problems + bulging fontanel
HIV Testing (7)
PCR, ELISA, Western Blot, Oral fluids test, ORASURE, rapid test, urine test
Antiretroviral treatment (5)
triple drug cocktail (attack virus in replication
prophylaxis/tx of opportunistic infections
vaccines
immune therapy
alternative tx
Post-exposure prophylaxis in HIV
- tx w/antiretroviral drugs after HIV exposure
- starts within 72 hrs, continue for month
- PEP showed 80% dec in HIV infections for occupational exposure
- concern for drug + sex exposure