[W5] Filoviruses

Question 1

How many species and families are included in Mononegavirales as of the document?

Answer 1

339 species in 11 families

Question 2

Name four human-pathogenic virus families within Mononegavirales.

Answer 2

• Filoviridae
• Paramyxoviridae
• Pneumoviridae
• Rhabdoviridae

Question 3

Give examples of viruses from the Filoviridae family.

Answer 3

• Ebola virus (EBOV)
• Marburg virus

Question 4

How many species and genera are in Filoviridae (as of 2020)?

Answer 4

11 species in 6 genera

Question 5

What is the structure of Filoviridae virions?

Answer 5

Helical ribonucleocapsid with envelope and glycoprotein spikes; ~80 nm in diameter

Question 6

What are the lengths of Marburg and Ebola viruses?

Answer 6

• Marburg: ~790 nm
• Ebola: ~970 nm

Question 7

What polymerase is packaged in filovirus virions?

Answer 7

RNA-dependent RNA polymerase (RdRp)

Question 8

What type of genome do filoviruses have?

Answer 8

Linear, non-segmented, -ssRNA (Baltimore Group V), 18–19 kb

Question 9

How many proteins are encoded by the filovirus genome?

Answer 9

7–9 proteins

Question 10

What are the genome features of filoviruses?

Answer 10

• Non-infectious alone
• 3’ and 5’ UTRs
• No cap or poly-A tail
• Not protein-linked

Question 11

What is the typical gene order in filoviruses?

Answer 11

3’-N-P-M-G-L-5’

Question 12

What are the functions of VP35 in EBOV?

Answer 12

• Polymerase cofactor
• Suppresses IFN
• Inhibits innate immune response

Question 13

What does VP40 do?

Answer 13

Major matrix protein; regulates virion shape, assembly, and budding

Question 14

What are the roles of GP (glycoprotein)?

Answer 14

• Mediates viral attachment and fusion
• Target for neutralizing antibodies

Question 15

What is the function of NP (nucleoprotein)?

Answer 15

Encapsidates RNA, essential for nucleocapsid assembly and RNA synthesis

Question 16

What does VP30 do?

Answer 16

Transcription activator; initiates mRNA synthesis and regulates replication switch

Question 17

What are the functions of VP24?

Answer 17

• Inhibits IFN signaling (blocks STAT1)
• Aids in assembly and condensation

Question 18

Which host receptor binds to EBOV phosphatidylserine?

Answer 18

TIM-1

Question 19

What is macropinocytosis?

Answer 19

Lipid raft-dependent endocytosis involving actin-driven membrane ruffles

Question 20

What triggers macropinocytosis during EBOV entry?

Answer 20

Apoptotic mimicry via TIM-1 and phosphatidylserine interaction

Question 21

What host conditions are required for GP-mediated fusion?

Answer 21

• Proteolysis
• Low pH
• Ca²⁺
• Binding to NPC1

Question 22

What happens during uncoating?

Answer 22

-ssRNA and replication enzymes are released into the cytoplasm

Question 23

Why must RdRp be packaged in EBOV virions?

Answer 23

Because the viral genome cannot be directly translated

Question 24

Where does RdRp initiate transcription in EBOV?

Answer 24

At the 3’ end of the genome

Question 25

What is polymerase stuttering and what does it produce?

Answer 25

Repeated slippage of RdRp, producing a poly-A tail on mRNA

Question 26

How is transcription regulated in EBOV?

Answer 26

Transcription shows polarity; downstream genes are transcribed less frequently

Question 27

What role does VP30 play in transcription?

Answer 27

Promotes transcription reinitiation at intergenic regions

Question 28

What is VP24’s role in transcription and replication?

Answer 28

Inhibits both processes by interfering with NP and polymerase function

Question 29

What is mRNA editing in filoviruses?

Answer 29

Insertion of residues by RdRp to create frame shifts for multiple protein products

Question 30

What is the role of sGP in EBOV?

Answer 30

A secreted glycoprotein that helps immune evasion

Question 31

What switches RdRp to genome replication mode?

Answer 31

Accumulation of nucleocapsid proteins

Question 32

What is the antigenome?

Answer 32

A full-length +ssRNA used as a template to synthesize -ssRNA genomes

Question 33

Where are spike proteins processed in EBOV?

Answer 33

On the rough ER and in the trans-Golgi via furin cleavage

Question 34

What does the M protein do during assembly?

Answer 34

Organizes virion assembly and recruits RNP

Question 35

How do EBOV virions acquire their envelope?

Answer 35

By budding from the plasma membrane

Question 36

What host system is required for EBOV budding?

Answer 36

The ESCRT machinery

Question 37

How are EBOV components transported to the assembly site?

Answer 37

* VP40 via endosomes * GP via secretory pathway * Nucleocapsid via cytoplasmic transport

Question 38

How does VP35 inhibit interferon production?

Answer 38

* Blocks RIG-I * Binds dsRNA * Acts as a decoy for IKKε and TBK1

Question 39

What does VP24 do in innate immune evasion?

Answer 39

Blocks nuclear import of phospho-STAT1

Question 40

What does sGP do in immune modulation?

Answer 40

Reduces TNF-α migration, acts as an anti-inflammatory agent

Question 41

How does VP35 inhibit adaptive immunity?

Answer 41

Prevents dendritic cell maturation

Question 42

How do survivors differ in immune response?

Answer 42

Show early cytotoxic T cell responses and higher T cell counts

Question 43

What structural features help EBOV evade antibodies?

Answer 43

* Large size * Mucin-domain glycosylation * Rapid macropinocytosis

Question 44

What is the potential role of sGP in humoral evasion?

Answer 44

May divert immune response by inducing non-neutralizing antibodies

Question 45

Why do filoviruses mutate rapidly?

Answer 45

Because RdRp lacks proofreading activity

Question 46

What is the approximate mutation rate of filoviruses?

Answer 46

Up to 1 per 1000 bases

Question 47

How does a high mutation rate benefit EBOV?

Answer 47

Increases genetic diversity and helps immune evasion

Question 48

When and where was Ebola virus first identified?

Answer 48

1976 in Zaire (now DRC), near the Ebola river

Question 49

What is the incubation period for EVD?

Answer 49

2 to 21 days

Question 50

What are common symptoms of EVD?

Answer 50

* Fever * Sore throat * Aches * Vomiting * Diarrhea * Rash * Sometimes internal bleeding

Question 51

What is the fatality rate of EVD?

Answer 51

50–90%

Question 52

How is EVD transmitted?

Answer 52

* Zoonotic spillover from fruit bats * Human-to-human via bodily fluids

Question 53

What cells does EBOV infect first?

Answer 53

Macrophages and monocytes

Question 54

How does EBOV cause hemorrhage?

Answer 54

Increases vascular permeability and activates coagulation

Question 55

How does EBOV affect dendritic cells?

Answer 55

Inhibits their maturation, preventing lymphocyte activation

Question 56

Which organ can EBOV damage via systemic spread?

Answer 56

The liver (via infected hepatocytes)

Question 57

What is the Ervebo vaccine?

Answer 57

A recombinant VSV-based Ebola vaccine approved in 2019

Question 58

Name another Ebola vaccine candidate in clinical trials.

Answer 58

cAd3-EBOZ (chimpanzee adenovirus vector) by GSK

Question 59

What is Inmazeb?

Answer 59

A monoclonal antibody cocktail targeting EBOV GP, used to treat EVD

Question 60

What are other therapeutic options explored for EVD?

Answer 60

* Mab114 * Remdesivir * Zmapp (Remdesivir and Zmapp had poor results)