RNA viruses

type of RNA virus, family, transmission, treatment

why is it had to make vaccines against RNA viruses?

• RNA mutates & make surface changes over time through “antigentic drift” which changes H & N proteins (in influenza)

how do RNA viruses replicate?

• they need to bring in machinery like reverse transcriptase & integrase to make a dsDNA from the RNA genome

what families are -ssRNA enveloped viruses?

• ARENAVIRIDAE: lassa fever, lymphocytic choriomeningitis (LCMV)

• BUNYAVIRIDAE: hantavirus

• DELTAVIRIDAE: hep D

• FILOVIRIDAE: ebola, marburg

• ORTHOMYXOVIRIDAE: influenza A, B, C

• PARAMYXOVIRIDAE: respiratory syncytical virus (RSV), mumps, measles

• RETROVIRIDAE: HIV 1 & 2, human t cell lymphocytic virus (HTLV) I & II

• RHABDOVIRIDAE: rabies

what species are a part of the retroviridae family?

• HIV 1 & 2

• HTLV I & II

• AIDS

how does HIV gain entry to the body? what does it bind to?

• GP120 binds to CD4+ cells

• GP41 binds to CXCR4

what are the stages of HIV replication?

1. binding

2. fusion: fusion of HIV to host cell via binding of coreceptors

3. reverse transcriptase: HIV RNA, reverse transcriptase, integrase & other proteins enter host cell & make dsDNA from ssRNA

4. integration

5. replication

6. assembly: new viral DNA that makes proteins collect in membrane, immature HIV forms

7. budding: new mature virion is released

what are the clinical phases of HIV?

• acute infection: 2-4 weeks after infetion

  • prodromal phase

  • flu like symptoms

  • antibody negative

  • very infectious

• clinical latency

  • asymptomatic for months-years

  • reproduction of virus is low

  • routine HIV testing

• acquired immunodeficiency disease (AIDS)

  • CD4+ cell count decreased below 200 cells/mm^3

  • cannot fight the infection as pts dont make good antibodies

define stages 0-3 of HIV

• stage 0: negative test within 6 months of testing positive, viral load is below the level of detection

• stage 1: CD4 t cells count >= 500 cells/uL

• stage 2: CD4 t cells 200-499

• stage 3: CD4 t cells <200, AIDS, present with bacterial infections

what treatment & prevention is there for HIV 1 & 2?

treatment:

• no vaccination because there are no RNA repair mechanisms & it is incorporated into our DNA

• drug treatment:

  • drugs that inhibit viral enzymes like reverse transcriptase

  • inhibit fusion

  • inhibit viral translation

  • anti-retroviral therapy

prevention:

• behavioral

• PrEP: pre-exposure prophylaxis

how is HIV transmitted?

• sexually, vertically, IV drugs, transfusion

describe HTLV I in terms of endemic, symptoms, transmission, treatment

associated with T cell leukemia & severe malignant lymphoproliferative disease of CD4+ cells (flower cells)

endemic: japan, caribbean, subsaharan africa, c & s america, middle east

symptoms: myelopathy/tropical spastic paraparesis (HAM/TSP)

• muscle weakness in legs

• urinary impotence

• spinal cord damage

transmission: sexually, vertically, IV drug use, transfusion

treatment: no vaccine

what families are a part of arenaviridae?

• lassa fever (viral hemorrhagic fever)

• lymphocytic choriomeningitis virus (LCMV)

how are arenaviridae transmitted?

zoonotic — rodent infected urine

what is the structure of arenaviridae?

sandy granular enveloped cells with ribosome-like structures

describe LCMV in terms if endemic, transmission, & treatment

-ssRNA enveloped - family arenaviridae

• endemic: europe, n & s america

• symptoms:

  • viral meningitis

  • <1% mortality

• transmission: inhalation of rodent urine

• treatment: rarely cause human infection, problematic in mice

describe lassa fever in terms if endemic, transmission, & treatment

• endemic: west africa

• symptoms: hemorrhagic fever, 5% mortality

• transmission: person-person exposure to infected fluids (rodent)

what viruses are a part of the bunyaviridae family?

• phlebovirus (rift valley fever)

• nairovirus (crimean congo hemorrhagic fever)

• bunyavirus (california encephalitis virus)

describe phlebovirus in terms if endemic, transmission, & treatment

bunyaviridae — rift valley fever

• endemic: africa

• symptoms: humans asymptomatic or fever, headache, muscle ache

• transmission: mosquitos & domestic cattle with acute viral illness

• treatment: no treatment

describe nairovirus in terms if endemic, transmission, & treatment

bunyaviridae — crimean congo hemorrhagic fever

• endemic: eastern europe to mediterranean

• symptoms: headache, fever, petechiae on tongue, jaundice

• transmission: tick borne

• treatment: supportive treatment

describe bunyavirus in terms if endemic, transmission, & treatment

bunyaviridae — california encephalitis virus

• endemic: midwest to northern central states

• symptoms: neurologic disease, viral meningitis

• transmission: mosquito

• treatment: supportive care

what virus is a part of the genus hantaviridae?

hantavirus (zoonotic - transmitted by rodent excreta

what is the only human-human strain of hantavirus?

andes strain

describe hantavirus & its strains in terms if endemic, transmission, & treatment

hantaviridae — hantavirus — rodent excreta

• sin nombre: four corners of southwest

• andes virus: south america - chile & argentina

  • pulmonary syndrome (HPS): emerging disease with fever, cough, GI symptoms, irreversible pulmonary edema, 38% mortality

• hantaan & seoul virus: far east

  • hemorrhagic fever with renal syndrome, multi organ failure

what genus is a part of the kolmioviridae?

deltaviridae — hep D

why is hep D considered an incomplete virus?

is requires another virus (Hep B) to replicate viral DNA & produce virions

what structure does deltaviridae have?

-ssRNA enveloped with helical nucleocapsid

describe deltaviridae in terms of symptoms, transmission, & treatment

• endemic: western africa/middle east

• symptoms: occurs in those infected or coinfected with HepB

  • jaundice, joint/abdominal pain, liver cancer

• transmission: blood or body exposure to mucous membranes

• treatment: no vaccine, HepB vaccine

what viruses are a part of the filoviridae family?

• marburg

• zaire ebola

describe the structure of zaire ebola

filoviridae

• 7 genes

• enveloped

• helical nucleocapsid

• distinct filamented morphology

describe zaire ebola in terms if endemic, transmission, & treatment

• endemic: subsaharan africa

• symptoms:

  • inc 8-10 days

  • fever, fatigue, abdominal hemorrhage

  • 70-90% mortality

• transmission: exposure to contaminated bodily fluids

• treatment: serum transfer, vaccination, Zmapp(mAB) - B cells that produce ebola cloned out of variable region & into constant human IgG

describe marburg virus in terms if endemic, transmission, & treatment

• endemic: africa

• symptoms:

  • inc 5-10 days

  • multi organ hemorrhage

  • 20-90% mortality

• transmission: exposure to contaminated body fluids

• treatment: supportive care

describe the shape/morphology of orthomyxoviridae

• 8 genes

• spherical enveloped virus

• protein spikes (peplomers) on surface that we make antibodies against that vary

• neuraminidase (virus exit): last protein cleaved that allows it to infect

• hemagglutinin (virus entry)

what viruses are a part of the orthomyxoviridae family?

• influenza a

• influenza b

• influenza c

describe influenza a

• 80% all infections

• pandemics/epidemics

• multiple subtypes on surface proteins (H1,2,3: N1, 2)

• infects humans, avian, swine

describe influenza b

• 20% of infections

• less severe epidemic

• human infection only

why is antigenic drift - reassortment a problem with influenza a?

• 2 different viruses infect the same cell & a new viral particle is produced (mixed with both viruses)

• 18 HA & 11 NA in avians

• how new strains occur

• so far, none have been person-person

describe orthomyxoviridae in terms of symptoms, transmission, & treatment

symptoms: target respiratory epithelial cells & damage

• secondary bacterial infection (pneumonia)

transmission: inhalation of aerosol/hand to mucous membrane

treatment:

• tri or quad vaccination

• tamiflu that targets neuraminidase & inhibits it

what viruses are a part of the paramyxoviridae family?

• human parainfluenza 1 & 3

• human parainfluenza 2 & 4

• mumps

• measles

• respiratory synctical virus (RSV)

all cause significant upper respiratory infection

describe human parainfluenza virus 1 & 3

paramyxoviridae

• 1 = croup

• 3 = bronchiolitis <2 years

describe human parainfluenza virus 2 & 4

2 = croup

4 = less severe infections not really detected in lab

describe mumps in terms of structure, symptoms & treatment

paramyxoviridae - 7 genes

• inc 16-18 days

• 40% infections subclinical

• infectious parotitis

• viral meningitis

• epididymis

• MMR or MMRV vaccine

describe measles in terms of structure, symptoms & treatment

paramyxoviridae - 6 genes

• 90% of people in contact who are not vaccinated with be infected

• infects epithelium of respiratory tract

• spread by cough/sneeze

• most infectious organism ever (11-18 people)

• complication = pneumonia

describe respiratory syncytial virus (RSV) in terms of structure, symptoms & treatment

paramyxoviridae - 11 genes

• young children most severe

• bronchitis

• lethal disease if cardiovascular deficiencies

• monoAB treatments that block attachment to epithelial, antivirals

what viruses are a part of rhabdoviridae?

rabies — zoonotic

describe rabies in terms of structure, transmission, symptoms, treatment

• enveloped bullet shaped virions, 5 genes

• transmission: exposure to infected saliva secretion, transplants

• causes:

  • prodromal: tingling sensations

  • furious: seizures, agitation, disorientation

  • dump: paralyzed, stupor, eventual coma/death

• treatment: vaccinations, HRIG

what viruses are +ssRNA enveloped & can produce viral protiens?

• coronaviridae: SARS-1, SARS-2, MERS

• flaviviridae: hep C, powassan, dengue, zika, yellow fever, west nile

• hepeviridae: hep E

• togaviridae: eastern equine encephalitis, rubella

how do we test for SARS? how do we create vaccinations?

• test for outer protein spikes

• create vacc against nucleoproteins

describe SARS-2 in terms of symptoms, transmission, treatment

coronaviridae - +ssRNA enveloped

• transmission: aerosol respiratory droplets

• symptoms: flu like, loss of taste, cardiovascular disease, vascular damage

• treatment: quarantine, immunosuppressive, antivirals, plasma therapy, vaccination

describe SARS-1 in terms of symptoms, transmission, treatment

coronaviridae - +ssRNA enveloped

• transmission: flu like

• symptoms: aerosol respiratory droplets

• treatment: quarantine, supportive care, antivirals

describe MERS-CoV in terms of symptoms, transmission, treatment

coronaviridae - +ssRNA enveloped

• transmission: camel to person, person-person

• symptoms: flu like, leukopenia, cell lysis/damage, hypoxemia

• treatment: quarantine

• 79 out of 182 infected = 44% mortality

what virus is a part of the hepeviridae family?

hep E (hepevirus)

describe hep E in terms of transmission, symptoms, & treatment

hepeviridae, hepevirus, +ssRNA enveloped

• transmission: fecal contamination of food & water

• symptoms:

  • 2-9wk inc

  • jaundice

  • liver damage

  • 10-30% mortality in pregnant women

    • fetal death

• treatment:

  • no vaccine, resolves on its own

  • supportive care

  • for pregnant women: IgM anti-HEV or IgG anti-HEV, quantitative load assays

why is hep E so dangerous for pregnant women?

20-25% of HEV pregnancies in 3rd trimesters result in maternal death due to viral replication in placenta, umbilical cord, & placental membrane

what viruses are a part of flaviridae family? how are they transmitted?

• yellow fever

• japanese encephalitis

• west nile

• dengue

• zika

• powassan (TICKS)

transmitted through mosquitos or ticks

describe yellow fever in terms of endemic, symptoms, treatments, transmission

flaviviridae

• endemic: africa & s america

• symptoms:

  • inc 3-6 days, almost all asymptomatic

  • 15% progress to jaundice

• transmission: mosquito

• treatment: vaccine or insect repellant

describe japanese encephalitis in terms of endemic, symptoms, treatments, transmission

flaviviridae

• endemic: western pacific & asia

• transmission: mosquito

• treatment: vaccine or insect repellant

• symptoms: fever, seizures, neurologic

  
  

describe west nile virus in terms of endemic, symptoms, treatments, transmission

• endemic: new england

• symptoms: 80% symptomatic

  • neurologic disease

• transmission: mosquito

• treatment: supportive care

describe zika in terms of endemic, symptoms, treatments, transmission

flaviviridae

• endemic: malaysia, s america

• symptoms:

  • death of brain tissue as fetus develops that kills neural cells

• transmission: congenital, sexual, blood transfusion

• treatment: supportive care

describe dengue virus in terms of endemic, symptoms, treatments, transmission

flaviviridae

• transmission: mosquito

• treatment:

  • supportive

• symptoms:

  • mild primary infection, low wbc

  • 4 strains, once infected with 1, protected for life, but if you come into contact with another, can cause more severe disease

  • dengue hemorrhagic fever: petechiae, fever, circulatory failure, shock, death

describe hep C in terms of endemic, symptoms, treatments, transmission

flaviviridae

• transmission: blood or body fluids

• symptoms:

  • 2-12 wk inc

  • jaundice/flu like

  • 70-80% become long term infection

  • cancer, death

• treatment:

  • no vaccine

  • antivirals for chronic infections

describe powassan virus in terms of endemic, symptoms, treatments, transmission

flaviviridae

• endemic: michigan, new york

• symptoms:

  • most asympt

  • progression to encephalitis = neuroinvasive disease, 50% permanent sequelae, 10% mortality

• transmission: black legged tick with rodents as carriers

• treatment: supportive