2013-02-08 VIR Arboviruses, Rubella and Parvovirus B-19

Question 1

What is phenotypic mixing?

What types of viruses does this process occur in?

Answer 1

two viruses infect same cell

some progeny are made that have the genome of one with (at least part of) the coat of the other

thus, you end up with phenotype that doesn’t make genotype

will go away within one generation as long as further co-infections are avoided

TYPES: “some arboviruses, polioviruses, -myxoviruses and some other viruses”

Question 2

What are arboviruses?

Which taxonomic groups have arboviruses?

Answer 2

not formal clade, just epidemiological classificaiton term for disease that are arthropod-borne virus

togaviridae, flaviviridae (the two we will consider) and also bunyaviridae (hantavirus! ahh!)

Question 3

While most togaviruses and flaviviruses are arboviruses, give an example of each family that are not.

Answer 3

rubella (togavirus)

Hep C (flavivirus)

Question 4

Describe the similarities between togaviruses and flaviviruses in terms of structure/nucleic acide, etc.

Answer 4

Both togaviruses and flavivirues are basically picornaviruses with an envelope (i.e. small, with single piece of (+)ssRNA for genome, with icosahedral symmetry)

Question 5

Describe the incubation processes for typical arboviruses.

Answer 5

Arboviruses undergo two incubations:

EXTRINSIC INCUBATION - in the vector (usually mosquito) for ~2 weeks leading to lifelong asymptomatic viremia in the arthropod

INTRINSIC INCUBATION - in the human host for ~1 week

Question 6

What is the serious disease caused by arboviruses?

Which strains cause it in the US?

Answer 6

Encephalitis

In US, caused by EEE, WEE, SLE, WNV California group of E’s ( and Venzuelan E virus sometimes seen in TX)

Question 7

Which of the two flaviviridae arboviruses would you rather have?

Answer 7

I’d rather have WNV than SLE

Question 8

Which of the two togaviridae arboviruses would you rather have?

Answer 8

I’d rather have WEE than EEE.

Question 9

What is the most common cause of encephalitis in the world?

Answer 9

Japanese encephalitis for which there is a vaccine

Question 10

Horizontal vs. vertical transmission

Answer 10

Vertical = mother to neonate

horizontal = everything else

Question 11

What are the two types of viral infection patterns in the neonate? What are their general characteristics?

Give examples of each

Answer 11

Perinatal—less big deal; generally like horizontal transmission in other peds pts (e.g. HIV, HBV, HSV2)

Transplacental—congenital anomalies not seen in horizontal trans of same virus; (e.g. parvovirus B-19, rubella, CMV, lymphocytic choriomeningitis)

Question 12

What defenses do fetuses have against viruses that manage to make it across the placenta?

Answer 12

1) maternal IgG
2) their own IgM after 4 mos
3) their own INF after 4 mos
4) maybe cell-mediated imm., too

Question 13

EEE

Family = ?

Epidem = ?

Trans = ?

Incubation = ?

Pathogen w/ s/sx = ?

Dx = ?

Prevention = ?

Tx = ?

Answer 13

Family = togaviridae (classified also as an arbovirus)

Epidem = only in summer/when mosquitoes are alive; mostly children affected; swampy areas and wetlands are worst hit; also kills local horses; mostly kids

Trans = mosquito—>bird*—>mosquit—>horse/human (DEAD END HOSTS)

*the bird is usually unaffected

Incubation = 1 week intrinsic incubation in host (2 week extrinsic incubation in vector)

Pathogen w/ s/sx = direct viremia (delivered from mosquito’s saliva to bloodstream); sudden onset severe headach, n/v, fever—>mental status ∆s—>seizures and nuchal rigidity—>TWO OPTIONS:

1) if you survive: high %—>severe neuro sequelae
2) if a severe case: paralysis—>coma—>death

—EEE usually causes the worst dz w/ ~50% fatality rate

Dx = isolate virus or incr titer

Prevention = kill mosquitoes; wear repellent; monitor mosquito traps via PCRing ground up dead ones; killed vaccine for horses is available

Tx = none

Question 14

Compare WEE to EEE

Answer 14

Western Equine Encephalitis

Family = togavirus

similar to EEE w/ higher incidence rate and lower death and permanent neuro sequelae rates; usually infants and adults >50 y/o

Question 15

SLE

Family = ?

Epidem = ?

Trans = ?

Incubation = ?

Pathogen w/ s/sx = ?

Dx = ?

Prevention = ?

Tx = ?

Answer 15

St. Louis Encephalitis

Family = flaviridae

Epidem = indigenous to North America more common in urban areas; adults >50y/o are most affected

Trans = maintained by bird—>mosq—>bird cycles w/ humans as DEAD END hosts

Incubation = again two: 1 week in humans two weeks in vector

Pathogen w/ s/sx = most infections inapparent but does cause moderately severe encephalitis w/ 10% fatality; sequalae uncommon

Dx = serologically

Prevention = no vaccine

Tx = no antiviral

Question 16

WNV

Family = ?

Epidem = ?

Trans = ?

Incubation = ?

Pathogen w/ s/sx = ?

Dx = ?

Prevention = ?

Tx = ?

Answer 16

Family = flaviviridae

Epidem = urban and rural; causes the most cases of viral encephalitis per year in US now; usually in folks over 60

Trans = birdmosquito—> human DEAD END host (also 10% via blood transfusion)

Incubation = same 2wks in vector 1wk in host

Pathogen w/ s/sx =

Dx = isolate virus from: brain tissue, blood, CSF or detect Abs in CSF or blood; PCR also available

Prevention = no vaccine; screen at bloodbanks

Tx = no antiviral

Question 17

Dengue

Family = ?

Epidem = ?

Trans = ?

Incubation = ?

Pathogen w/ s/sx = ?

Dx = ?

Prevention = ?

Tx = ?

Answer 17

Family = flavivirus

Epidem = subtropics and tropics S.E. Asia and Caribbean

Trans = Aedes aegypti—>humans—>A. aegypti (i.e. humans are NOT dead ends!)

Incubation = 1 week in host

Pathogen w/ s/sx = fever, severe retro-orbital headache, myalgia and arthralgia (“break-bone” fever”) and rash

—Dengue Hemmorrhagic fever in those native to endemic areas (likely b/c there are 4 cross-reacting antigenic types); severe/fatal: 2nd infection immune complexes form and then either a) activates complement cascade—>incr vasc perm + thrombocytopenia OR b) virus penetrates monocytes and macrophages—>release hella cytokines

—point: hemorrhage—>hematemesis—>shock—death

Dx = isolate—>cell culture or IgM or 4X IgG at convalesecent vs. acute phase

Prevention = no vaccine; insecticides, drain stagnant water, personal protection

Tx = no antiviral

Question 18

La fièvre jaune

Family = ?

Epidem = ?

Trans = ?

Incubation = ?

Pathogen w/ s/sx = ?

Dx = ?

Prevention = ?

Tx = ?

Answer 18

Family = flavivirus (w/in arbovirus grouping, too)

Epidem = endemic to rural tropical Africa and South America; can cause import epidemics in U.S., etc.

Trans = Aedes aegypti—>humans—>A. aegypti (i.e. humans are NOT dead end host)

Incubation = 1 week in host, 2 weeks in vector

Pathogen w/ s/sx = instant viremia due to direct injection by mosquito—>multiplies in vasc endothelium—>worsen viremia—>liver, kidney, spleen—>fever, jaundice, n/v w/ hematemesis

—high mortality, occasional subclinical cases

Dx = PCR of plasma specimen

Prevention = 17-D vaccine is live-attenuated and gives great protection

Tx = ?

Question 19

Parvovirus B-19

Family = ?

Epidem = ?

Trans = ?

Incubation = ?

Pathogen w/ s/sx = ?

Dx = ?

Prevention = ?

Tx = ?

Answer 19

Family = parvoviridae

Epidem = super common; 50% adults are seropoz

Trans = can go transplacentally

Incubation =

Pathogen w/ s/sx = RBC precursor tropism—>inhibits RBC synth for ~1 week

—usually just leads to ERYTHEMA INFECTIOSUM w/ sometimes a TRANSIENT ARTHRITIS

—can lead to TRANSIENT APLASTIC CRISIS in pts with pre-existing erythrocytopenia (e.g. sickle); fatal w/o transfusion tx

—HYDROPS FETALIS occurs when transplacental route occurs in 1st or 2nd trimester; still can cause fetal demise (just w/o the hydrops fetalis) in 3rd trimester; massive increase in CO b/c anemia leads to edema, etc.

Dx = IgM (would not be present in immunocompromised pts so PCR from blood); fetal infection use PCR of amniotic fluid

Prevention = none

Tx = pool Ig for chronic/immunocomp. pts

Question 20

Rubella

Family = ?

Epidem = ?

Trans = ?

Incubation = ?

Pathogen w/ s/sx = ?

Dx = ?

Prevention = ?

Tx = ?

Answer 20

Rubella (a.k.a. “German Measles”)

Family = togavirus (though NOT arbovirus)

Epidem = less contagious than measles; near-universal vaccination in U.S.—>last case 2005

Trans = resp drops (spread one week before and after rash!)

Incubation = 18 days

Pathogen w/ s/sx = resp epithel—>viremia; 3 days of rash w/ fever and lymphadenopathy; even subclinical cases—>lifelong immunity

—TRANSPLACENTAL: cataracts, PDA, deafness, MR; less and less a risk as you move along in pregnancy

Dx = ?

Prevention = live-attenuated vaccine (in MMR); major purpose is to prevent congenital rubella

Tx = ?

Question 21

togavirus

Nucleic acid set-up?

Virion structure?

How does it multiply?

Examples?

Answer 21

NA = single (+)ssRNA

virion = icosahedral enveloped

REPLICATION:

1) uncoats in cytosol, 2) (+)ssRNA genome is translated into several structural and non-structural proteins (i.e. not just one large polypeptide like poliovirus), 3) makes RDRP to make (-)ssRNA template of its genome, 4) buds out through plasmalemma

EXAMPLES: rubella, arboviral encephalitises (WNV, EEE, WEE, etc.)

Question 22

parvovirus

Nucleic acid set-up?

Virion structure?

Replicaiton ?

Examples?

Answer 22

NA = single, linear ssDNA

virion = smallest human virus; icosahedral naked

Replication: adsorption—>moves to nuc for replication—>ssDNA has “hairpin loops” that ~=dsDNA where cell’s DNA pol’s synth progeny genomes—>mRNA from dsDNA intermediate by cell’s RNA pols—>assembled in nucleus

EXAMPLES: B-19 (slapped cheeks)

Question 23

Flaviviruses

Nucleic acid set-up?

Virion structure?

How does it multiply?

Examples?

Answer 23

NA = (+)ssRNA

virion = enveloped

REPLICATION:

1) rep in cyto
2) translate RNA genome into large polyprots
3) cleaved by virion-encoded proteases

Examples: HCV, plus several arboviruses including- Yellow Fever, Dengue, West Nile, St. Louis and Japanese encephalitis