+Strand RNA Viruses

Question 1

explain why RNA alone from a +strand RNA virus is infectious?

Answer 1

the +strand RNA is already like mRNA used in human cells, so it can be directly translated by ribosomes

viral proteins translated as polyprotein (1 long peptide) that is cleaved into proteins post-translationally

Question 2

Which of these families of +strand RNA viruses are NON-enveloped?
a. Caliciviridae
b. Flaviviridae
c. Picornaviridae
d. Togaviridae
e. Coronaviridae

Answer 2

NON-enveloped:
a. Caliciviridae
c. Picornaviridae

enveloped:
b. Flaviviridae
d. Togaviridae
e. Coronaviridae

Question 3

Within the Picornaviridae (non-enveloped) +strand RNA virus family is Enteroviruses, Rhinoviruses (and Hep. A). Enteroviruses and Rhinoviruses are morphologically similar but cause very different diseases - explain the difference

Answer 3

Enteroviruses: via fecal-oral, cause GI illness, acid stable, grow at body temp

Rhinoviruses: via respiratory drops, acid labile, grow at temp of nose

Question 4

how are the majority of Togaviridae and Flaviviridae transmitted? (both enveloped +strand RNA virus families)

Answer 4

arboviruses - transmission via arthropod (for most)

Question 5

do virions of +strand RNA viruses contain viral enzymes?

Answer 5

no! all proteins are made once the virus enters the host cell (remember its RNA can be directly translated by ribosomes - “infectious RNA”)

Question 6

what shape is poliovirus? is it enveloped?

Answer 6

Poliovirus: icosahedral, naked (entry via receptor-mediated endocytosis), +ssRNA

[picornaviridae family]

Question 7

what is unique about poliovirus RNA and how does it disrupt host protein synthesis?

Answer 7

no 5’ cap, 5’UTR is long and contains IRES (internal ribosomal entry site)

viral protease cleaves host protein needed to scan for AUG initiation codon

viral protein synthesis continues because it is cap-independent, while host protein synthesis is halted

[recall polio is +ssRNA]

Question 8

explain the function of RNA-dependent RNA polymerase (RDRP) as found in poliovirus

Answer 8

viral proteins made from +strand RNA in poliovirus, using host ribosomes

one of these proteins is RNA-dep RNA pol: enzyme which uses (+)strand RNA as template for (-)strand RNA

(-)strand RNA created then serves as template for (+)strand RNA

newly made (+)strand RNA (made in excess over -strand) is assembled into particles and released as new viruses (cells are killed via lysis)

[recall polio is +ssRNA]

Question 9

explain the polio paradox

Answer 9

used to be (very long time ago) very common and infectious, so most people developed memory cells for life-long immunity (newborns had Abs from mother)

when hygiene improved, wild polio became less prevalent in environment and polio began to become epidemic (no maternal Abs)
(until the vaccine was developed)

Question 10

how is poliovirus (+ssRNA) transmitted and what kind of illness does it typically cause?

Answer 10

poliovirus: enterovirus spread via fecal-oral, 95% cases restricted to GI tract with asymptomatic infection

4% have minor illness, nonspecific symptoms (“abortive poliomyelitis”)

1% develop meningitis or flaccid paralysis (Paralytic Poliomyelitis) if virus travels to CNS

Question 11

what 3 vaccines are available for poliovirus (+ssRNA)? contrast them

Answer 11

1. Salk/IPV (inactivated polio vaccine): inactivated, killed
2. Sabin/OPV (oral polio vaccine): live, attenuated, can revert to wild polio, can spread, now used only in developing countries - allows for transmission from vaccinated children to non-immune contacts (safe as long as they are not immunocompromised)
3. eIPV (enhanced IPV): less recombination with wild type virus, less vaccine induced cases

Question 12

what family of viruses do Coxsackievirus, Echovirus, Enterovirus, and Norwalk belong to, and what types of illness do they typically cause?

Answer 12

all Enteroviruses belonging to Picornaviridae (+ssRNA, nonenveloped icosahedral)

Coxsackievirus and Echovirus - conjunctivitis, febrile rash, meningitis, hand/foot/mouth disease

Enterovirus - GI
Norwalk - GI, cruise-ship diarrheal outbreaks

Question 13

which enterovirus is most often associated with diarrheal outbreaks on cruise ships?

Answer 13

Norwalk (non-enveloped +ssRNA)

Question 14

contrast the genome, transmission, and disease type (acute/chronic) of:
a. Hep A
b. Hep B
c. Hep C
d. Hep D
e. Hep E

Answer 14

a. Hep A (picornavirus): +ssRNA, fecal-oral, acute disease

b. Hep B (hepadnavirus): dsDNA, blood, chronic disease (carcinoma)

c. Hep C (flavivirus): +ssRNA, blood, chronic disease (carcinoma)

d. Hep D (deltavirus): +ssRNA, blood, basically just enhances HBV infection

e. Hep E (calicivirus): +ssRNA, fecal-oral, acute disease, rare in USA

Question 15

which 2 forms of hepatitis are associated with carcinoma?

Answer 15

HBV (dsDNA) and HCV (+ssRNA)

Question 16

which form of hepatitis is rare in the USA

Answer 16

HEV (Calicivirus): +ssRNA, fecal-oral, acute self-limiting disease, RARE in USA

Question 17

Flaviviridae and Togaviridae families are similar in that they are _____ shaped, [nonenvelope/enveloped] +ssRNA, and mostly _____-borne

Answer 17

Flaviviridae and Togaviridae families are similar in that they are ICOSAHEDRAL shaped, ENVELOPED (from internal organelles) +ssRNA, and mostly ARTHROPOD-borne

Flaviviridae includes flaviviruses and Hep C

Togaviridae includes alphaviruses and rubivirus (Rubella)*
*note Rubella is kind of its own thing

Question 18

contrast Eastern, Western, and Venezuelan Equine Encephalitis viruses, alphaviruses belonging to the Togaviridae family (enveloped +ssRNA, icosahedral)

Answer 18

Eastern Equine Encephalitis: birds—> mosquitos/horses (humans dead-end), rare, 50% fatal

Western Equine Encephalitis: birds—> mosquitos/horses (humans dead-end), less severe/more frequent

Veneziuelan Equine Encephalitis: rodents—>mosquitos/horses (humans dead-end), flu-like disease

Question 19

what is the most severe form of Equine Encephalitis? what kind of virus is this?

Answer 19

Eastern Equine Encephalitis Virus: type of alphavirus (of Togaviridae family, icosahedral/enveloped +ssRNA), rare, 50% fatal

birds—>mosquitos/horses (humans dead end)

[recall the other forms are Western and Venezuelan]

Question 20

what kind of virus is Chikungunya Virus (including what type/family it belongs to) and what kind of symptoms does it cause? where does it come from?

Answer 20

Chikungunya virus: alphavirus of togaviridae family (icosahedral, enveloped +ssRNA)

humans (primates) to mosquitos

—> fever, joint pain/swelling, muscle pain, rash - self-limiting but can last for months

Question 21

how is Rubivirus (Rubella) transmitted, and why was it added to the MMR vaccine?

Answer 21

Rubella: part of togaviridae family (icosahedral, enveloped, +ssRNA)

respiratory transmission —> “German measles”: rash beginning on face and spreading + non-specific respiratory symptoms, self-limiting

added to MMR because of Congenital rubella syndrome - can cause stillbirth/miscarriage/birth defects (esp. during 1st trimester)

Question 22

what virus causes German Measles and what type of vaccine is available for this virus?

Answer 22

Rubivirus (Rubella): enveloped +ssRNA

MMR vaccine: live attenuated vaccine

[recall that MMR vaccine is important for preventing congenital rubella syndrome - serious birth defects of fetal death]

Question 23

for which of these Flaviviruses (icosahedral, enveloped +ssRNA) are humans accidental hosts?
a. Dengue Virus
b. Saint Louis Encephalitis Virus
c. Zika Virus
d. Yellow Fever Virus
e. Japanese Encephalitis Virus
f. West Nile Virus

Answer 23

hint: the viruses named after places are those in which humans are accidental hosts

b. Saint Louis Encephalitis Virus
e. Japanese Encephalitis Virus
f. West Nile Virus

Question 24

what virus does this describe?
- enveloped, +ssRNA
- found in Asia and western Pacific
- transmitted via mosquitos to pics/aquatic birds (humans dead-end)
- very few infected people develop self-limiting illness, but there is potential for serious neurological manifestations
- inactivated vaccine available

Answer 24

Japanese Encephalitis Virus: type of Flavivirus (key identifying feature is location)

symptoms usually self-limiting: nonspecific fever, aseptic meningitis, encephalitis

possible severe CNS manifestations: acute encephalitis (most common), seizures (children), acute flaccid paralysis, etc

Question 25

who is most at risk for serious complications of Saint Louis Encephalitis Virus? What kind of virus is this?

Answer 25

Saint Louis Encephalitis Virus: flavivirus (enveloped, +ssRNA), mosquitos to birds (humans dead end)

very few have symptoms

elderly patients at risk for severe CNS disease - encephalitis, stiff neck, meningitis, coma

Question 26

what kind of virus is West Nile Virus? where does it come from?

Answer 26

West Nile Virus: flavivirus - enveloped, icosahedral, +ssRNA

mosquitos to birds (humans dead-end)

mostly self-resolving symptoms (muscle weakness, confusion, headaches, rash, nausea)

can cause severe neurological disease with high fatality (10%, encephalitis and paralysis) - most severe for >60 years of age!

Question 27

what virus does this describe?
- enveloped, +ssRNA
- causes “break-bone fever”
- transmitted from mosquitos to monkeys/humans
- can develop shock syndrome due to antibody-mediated enhancement

Answer 27

Dengue virus: flavivirus (enveloped, +ssRNA), mosquitos—>humans

break-bone fever: severe joint/bone pain

shock syndrome: 4 serotypes of Dengue virus but neutralizing Abs do not cross react (bind other serotypes but cannot neutralize) —> rise in immune complexes, complement activity, cytokine release, etc

Question 28

what kind of virus is Yellow Fever and what symptoms does it cause?

Answer 28

Yellow Fever virus: flavivirus (enveloped +ssRNA), Africa and South America

—> jaundice + fever (YELLOW FEVER), headache, myalgia (muscle pain)

high mortality via dissemination —> shock and hemorrhage

Question 29

where is Yellow Fever found and what kind of vaccine is available for it? (Flavivirus, enveloped +ssRNA)

Answer 29

Yellow fever: mosquitos —> monkeys/humans in Africa and South America

live attenuated vaccine available

[recall Yellow Fever has high mortality due to shock and hemorrhage]

Question 30

Which Flavivirus (enveloped, +ssRNA) is transmitted via the Aedes mosquito and typically causes only mild symptoms, except during pregnancy, in which it can cause microcephaly and severe fetal brain defects?

Answer 30

Zika virus: enveloped, +ssRNA

usually mild symptoms: fever, rash, arthralgia, conjunctivitis

pregnancy: microcephaly, severe fetal brain defects

Question 31

who is at risk for serious complications from Zika Virus (flavivirus, enveloped +ssRNA)?

Answer 31

major issue during pregnancy - can cause microcephaly or severe fetal brain defects

other than that, causes mild symptoms (fever, rash, arthralgia, conjunctivitis)

Question 32

which form of Hepatitis is curable with medication?

Answer 32

only Hepatitis C: flavivirus (+ssRNA, enveloped), transmitted via blood

Question 33

what are the clinical manifestations of untreated Hepatitis C virus (flavivirus, +ssRNA, enveloped)?

Answer 33

acute hepatitis —> chronic hepatitis and cirrhosis (mostly due to immune response) —> hepatocellular carcinoma (hepatocytes growing quickly to repair damage, tumors form)

chronic infection sheds virus for years

*however recall this type of Hepatitis is curable with medication!

Question 34

what shape is Coronaviridae?

Answer 34

helical nucleocapsid with glycoprotein spikes forming a “corona” (crown)

respiratory transmission, mostly asymptomatic

cause of SARS, MERS, COVID (ACE2 receptor)