Lecture 7 - Mpox Flashcards
What is the family and genus of Mpox
Family - Poxviridae
Genus - Orthopoxvirus
What is Mpox
- Viral zoonotic disease in tropical rainforests
- Occurs sporadically in Central/West Africa’s tropical rainforest
- Symptoms similar to smallpox but with less severity
Structure of Mpox
- Largest viruses excluding giant viruses
- dsDNA genome (190,000bp)
- More than 200 polypeptides - many target immune response
- Brick shaped - dumbbell core (contain nucleic acid), lateral bodies (unknown function)
- Enveloped - resistant to inactivation
- Replicate in cytoplasm
- Explored as Gene therapy vectors
History of Mpox
1958 - two outbreaks of pox-like disease in crab eating monkeys in Statems Serum Insitiut in Copenhagen
1970 - Identified in 9 year old boy from Democratic Republic of Congo
Remains endemic in Central/West Africa
Two clades of Mpox
Central African Clade (Clade 1)
West African clade (Clade 2, IIa and IIb) - sequence similarity is over 99%
Natural reservoir of Mpox
Unknown
thought to be African rodents and small mammals
Human infection thought to be caused by handling infected monkeys, tree squirrels, Gambian rats and striped mice
Mpox has been isolated twice from nature
First - Ill African Rodent in DRC - 1958
Second - dead infant Mangabey in Tai national park - 2012
2017 Nigeria Outbreak
- Largest ever outbreak
- Cluster of cases (two brothers, uncle and neighbour) fell sick after eating an infected monkey
- 244 cases across 25 states and FCT of Nigeria
- Six deaths
- 75% cases male and aged 21-40
Cases outside Africa
USA - 2003:
53 people infected with west African clade from prairie dogs transported from Ghana
2018-2021:
No fatalities but 1 case in Israel, 1 case in Singapore, 7 in UK - 5 were returning from Nigeria
Current situation of Mpox
90574 cases in total
26703 cases across 29 European countries
As of 2024, majority of EU countries have not reported a new case in three weeks, and 12 countries have not reported one for more than 30 days
Mpox virus distribution by clades
Nigerian 2022 outbreak was caused by lineage B.1 of west African clade
Evolution continues
D209N, P722S, and M1741I are all non-synonymous SNPs found on surface protein B21R - Enhancing transmissibility
Mpox Life cycle
Virus exists in two infectious forms: Extracellular Enveloped Virion (EEV) and Intracellular mature virion (IMV) which differ in surface glycoproteins
- EEV attaches and enters cell
- EEV uncoats leading to early gene expression or a second uncoating’
- Intermediate gene expression takes place or DNA replication immediately takes place to form viral factory
- Viral factory leads to late gene expression and assembly of progeny virions
- Viral factory form immature virions which then form intracellular mature virions
- Intracellular mature virions bud through trans-golgi to form Intracellular enveloped virions
- Intracellular enveloped virions leave cell to form cell-associated enveloped virions which then form extracellular enveloped virions
Immune evasion of Mpox virus
Encodes proteins involved in intrinsic, adaptive and innate immunity.
West African clade II - no expression of complement-modulating proteins
Central African Clade I - Encode for monkeypox inhibitor of MOPICE that inhibits complement activation by binding C3 and C5 convertases.
Transmission of Mpox
Animal to human - bites and scratches, handling animal products
Human to human - Skin to skin contact, Indirect contact via bedding/clothing, close respiratory tract, mucous membrane, broken skins, placenta
4 stages of progression
Stage 1 - Incubation (5-21 days)
- No symptoms
- Virus in bloodstream at end of period
Stage 2 - Febrile stage (1-4 days)
- Fever, Swollen lymph nodes, headache, chills, sore throat etc
- Virus in blood
- Small lesions in mouth at end of stage
Stage 3 - Rash stage (2-4 weeks)
- Virus may still be in blood
- Virus in skin lesions
- Antibodies produced and detectable
Stage 4 - Recovery
- Patient recovers and specific antibodies still present
- Scars remain
Vaccination for Mpox
- Smallpox eliminated in 1977 by mass and targeted vaccination
- 1980, WHO announced smallpox eradication
Types of smallpox vaccines for Mpox
ACAM2000 - live vaccinia virus
Modified vaccinia Ankara (MVA) - 2 doses 4wk apart - no lesion- no replication so safe in immunocomprimised people
LC16m8 - Single-dose - Less replication than ACAM2000, and so safer
Antivirals for Mpox
Cidofovir
Brincidofovir
Tecovirimat
Vaccinia immune globulin
