Poxvirus

B19 infection during pregnancy

- 1st trimester: death - 2nd trimester: hydrops fetalis- anemia and congestive heart failure

genus dependovirus

- AAV is a parovirus that infect humans, but requires a helper virus, like adenovirus - no clinical disease associated with infection- used for gene therapy - found with high frequency in school aged children and families - integrates into chromosomes, kills and lyses cells to spread

Parovirus epidemiology

- B19 infection is common worldwide: nearly 90% of adults over 50 are IgG+ - spread is likely via close contact, fomites or droplets from active case: - especially in families, classrooms - virus can be transmitted by blood - enters primarily by respiratory route - vertically from mother to fetus - tropism for erythroid (RBC) pregenitor cells

emerging pox disease

- MCV - monkeypox, MPX - cantaglo- vaccinia (Brazil) - Cowpox, CPX- from cats and rats - Bioterroism- smallpox - many unclassified poxviruses are discovered each year - need improved vaccines and drug therapy

fifth disease

- acute, benign contagious exanthem of children - viremia 6-8 days post infection - during viremia: fever, malaise, itching - rash may appear after viremia, can spread from face (slapped cheek) to trunk, limbs

smallpox vaccine complications

- autoinoculation, spread to close contacts - generalized vaccina- rash - eczema vaccinatum- contraindicated - accidental infection of other sites: eye (keratoconjunctivitis) - post vaccinial encephalitis - myopericarditis - progressive vaccinia- immunocompromised - loss of fetus- contraindicated - CDC: 1/1000 serious reactions, 1 deaths/million - vaccination programs discontinued mostly

What do poxvirus and parvovirus have in common

- both have DNA genomes - in general, wont see may cases of either except for B19 parvovirus and Molluscum contagiosum poxvirus

aplastic crises

- can complicate chronic hemolytic anemia, adults (sickle cell anemia)

smallpox

- caused by Variola virus (species) - severe generalized disease- killed about 500 million, in 1900s (about 75 years) - occurred worldwide until vaccination campaign eradicated disease. 1979 WHO certified the world free of endemic smallpox - In 1796, Jenner showed that inoculation with cowpox protected against smallpox (variola) vaccination from "vacca", cow, but vaccinia is NOT cowpox

Lab diagnosis poxviruses

- characteristic skin lesions and rash - collect specimens from "crusts" and vesicular fluid, nasal secretion - smallpox, monkeypox, cowpox, growth in cell culture, detection of viral antigens or PCR detection of genome, EM of lesion - molluscum contagiosum: charcteristic lesions, histological detection of inclusion bodies in epithelial cells, no cell culture

conclusions about HBoV

- circulating in US - associated with both upper and lower respiratory tract disease in infants and young children

Orf

- disease of sheep and goats, worldwide - can be transmitted to humans by direct contact - in humans, lesions at site of abrasion, self-resolving, recovery results in immunity lesions often on hands

generalized poxvirus infection

- entry by direct contact: aerosol - spread, primary or secondary viremia - disease: internal organs especially lungs, skin lesions - ex: smallpox, human monkeypox

What does HBoV cause

- fever - rhinorrhea - wheezing - observed in more than 50% - 70% had abnormal chest x-ray - seasonal distribution

Parvoviruses "parvus", small

- found in wide range of animals - Human viruses associated with disease- genus parovirus (no human yet), genus erythrovirus (parvovirus B19), genus dependovirus (AAV), genus amdovirus (no human yet), genus Bocavirus (human bocavirus, HBoV, respiratory infections in lungs

Molluscum contagiosum, MCV

- found worldwide - human only reservoir - transmitted by direct contact or fomites, STD - self limited lesions, pearly white and painless, clusters of 5-20 nodules, limited to epidermis, but NOT on palms and soles - may take months-years to resolve - common in children and immunocompromised (>300,000 doctor visits/year in US)

monkey pox

- genome similar to smallpox and vaccinia - causes disease with similar to smallpox - monkey reservoir (squirrels, rodents), zoonotic - found in Africa - transmitted to humans by direct contact with prarie dogs in US in 2003 outbreak

cowpox

- genome similar to smallpox and vaccinia - mild disease of cows (zoo animals, cats) - rodent reservoir - transmitted to humans by direct contact during milking, often on hands

Chickenpox or varicella zoster is what kind of virus

- herpesvirus (not poxvirus)

eradication of smallpox

- host range restricted to humans: no animal reservoir - single stable serotype even though there are 2 types: variola major (high mortality 30% average) and variola minor (low mortality 10%) - effective vaccines can be made from animal poxviruses (vaccina viruses) - consistent and distinctive disease presentation - stable, cheap, easy to administer vaccine - vaccination indicated by scar - WHO vaccination program

arthopathy

- immune complexes can cause arthralgias, especially in adolescents and adults - especially in proximal interphalangeal and metacaropphalangeal (knuckle) joints

Timecourse of parovirus B19 infection

- incubation: days 1-6, cold like symptoms - lytic infection stage: day 5-15, virus rapidly growing, IgG present - non-infectious immunologic phase: day 21-28, rash, IgG present

Poxvirus structure and virion characteristics

- large and stable virion characteristics 1. brick or ovoid shaped 2. complex structure- multiple membranes surround core 3. linear ds DNA genome: 130-380 kbp encodes 150-300+ proteins

localized poxvirus infections

- main site of initial infection and lesion: back of hand (where skin is thin) - occasional lesion on face +/- genitals - rare generalized disease +/- encephalitis - ex: human cowpox, Orf, vaccinia, molluscum

smallpox vaccine (vaccinia) will protect against orthopoxvirus- smallpox, monkeypox and cowpox but not against which different pox genera

- molluscum contagiousum - Orf virus

human bocavirus (HBoV)

- newly identified human parovirus - infants and children <2 years old - respiratory specimens tested negative for respiratory syncytial virus, parainfluenza viruses (type 1-3), influenza A and B viruses, and adenovirus - screening for it uses polymerase chain reaction (PCR) - results: 5.2% who had a respiratory specimen submitted postive for HBoV

Lab diagnosis of parovirus

- not grown in conventional cell culture - tests for viral DNA in serum or tissue samples: dot blot hybridization, In situ hybrid (ISH), PCR - Tests for B19 specific IgM and IgG available: No treatment or prevention for humans now (Blood transfusion for anemia), there is a vaccine for dog/cat parvovirus

most have ds genomes, icosahedral symmetry and replicate in the nucleus, EXCEPT Paraviridae and Poxviridae. What is different about them?

- parvoviridae has a ss genome - poxviridae has complex structure and replicates in the cytoplasm

poxvirus vs. parvoviruses

- poxviruses: largest of all viruses - parvovirueses: one of the smallest viruses

Clinical symptoms of smallpox

- smallpox simultaneous: all lesions are in one or are at the same stage - varicella (chicken pox)- successive crops, different stages of lesion - infections are symptomatic: characteristic rash and "pox" - day 1-3: pre eruption phase - days 6-10 papules and pustules - day 11-14: scabs

zoonosis

- spread from animals to humans

paroviruses virion, structure

- they are small (18-26 in diameter) - ss, linear DNA genome (about 5000 bp) - they are tough, resistant to heat, pH extremes, non-enveloped, icosahedral symmetry - negative sense and positive sense strands packaged separately

B. Parvovirus (B19) replication

- transcription, replication, and assembly take place in the nuclei of dividing cells; especially erythroid derived cells - requires host factors and DNA polymerases - release of virus occurs by cell lysis- no envelope - gets in and replicates in nucleus - proteins translated in cytoplasm - gets out of cell by lysis

vaccina- vaccination for smallpox

- vaccination stoped in 1970s- vaccine has serious side effects in some people - about 160 million unvaccinated people in US: those vaccinated may no longer be immune, military personnel are vaccinated, first responders - but vaccination right before or just after exposure can afford some protection - must get a blister/scab called a "take" for the vaccine - most effective vaccine story ever - tissue culture Acam 2000 is used

Replication cycle of poxvirus

- virus goes in - early transcription - late- leads to late proteins - all occurs in cytoplasm- using own enzymes - no splicing because occurs in cytoplasm not nucleus - begins virion assembly - when it buds, it loses membrane

B19 pathogenesis and immunity

- virus is difficult to isolate - day 5-15, viremia - day 10- IgM increases - day 16- IgG increases

epidemiology of poxvirus

- virus is transmitted by contact with an active case or fomites (objects) - humans (molluscum or smallpox) - zoonosis- animals (cows, sheep, goats, cats, rodents)

B19 diseases

-fifth disease (erythema infectiosum) -B19 infection during pregnancy -Aplastic crises - arthropathy

Poxviruses with animal reservoirs

-monkeypox -cowpox - Orf - Yaba Tumor Virus - Tanapox virus

DNA viruses

HHAPPPPy viruses - Herpes - Hepadna - Adeno - Papova: papillamoviridae and polymaviridae - Parvo - Pox

erythema infectiosum

slapped cheek appearance characteristic of fifth disease

What was the first disease that was controlled by immunization and the first (only) viral disease that has been eradicated?

smallpox (live vaccinia virus)

pathogenesis and immunity to poxvirus

smallpox (variola, extinct) and monkey pox (extant- still found in nature) - infection through droplets or fomites - primary infection is of upper respiratory tract with primary viremia, then spread to secondary targets including liver, spleen, bone marrow or lungs. Secondary viremia and infection of skin - if recovery occurs, virus is eliminated - survival of natural pox infection results in life long immunity ( to virus in same Genus) other poxviruses generally cause localized infections, transmission by direct contact with lesion

Better Poxvirus vaccine options

underdevelopment - modified vaccinia ankara (MVA): 6 deletions in genome, no reversion to virulence, attenuated, poor growth in mammalian cells, host range mutant- used for cancer vaccines - also may use canary pox, fowlpox- HIV success story - targeted deletions in virulence genes

prevention of poxvirus infections

vaccination recommended for those working with or exposed to orthopoxviruses: US military, smallpox response teams, health care workers - it works for smallpox, monkeypox, cowpox, but NOT orf, molluscum, yaba, or tana-pox decontamination - standard disinfectants for surfaces - hot water and bleach for exposed clothing and linens