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Questions and Answers
What role does the minor nucleocapsid protein VP30 play in Ebola virus mRNA synthesis?
What role does the minor nucleocapsid protein VP30 play in Ebola virus mRNA synthesis?
What happens to transcription if the stem-loop structure at the beginning of the NP gene is disrupted?
What happens to transcription if the stem-loop structure at the beginning of the NP gene is disrupted?
Which viral protein is the most abundant and associated with the viral envelope in the filoviruses?
Which viral protein is the most abundant and associated with the viral envelope in the filoviruses?
What is the primary function of VP40 in the context of viral structure?
What is the primary function of VP40 in the context of viral structure?
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What suggests the possibility of latent infection in survivors of Ebola virus infection?
What suggests the possibility of latent infection in survivors of Ebola virus infection?
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What term describes the recurrence of disease after a period of inactivity in the context of Ebola virus infection?
What term describes the recurrence of disease after a period of inactivity in the context of Ebola virus infection?
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Which cellular proteins may interact with VP40 to form virions at the plasma membrane?
Which cellular proteins may interact with VP40 to form virions at the plasma membrane?
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What is suggested as a potential preventive measure against disease recrudescence in Ebola virus survivors?
What is suggested as a potential preventive measure against disease recrudescence in Ebola virus survivors?
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What is the role of the 3’ leader in the viral genome?
What is the role of the 3’ leader in the viral genome?
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How does the viral RNA polymerase begin the transcription process for filoviruses?
How does the viral RNA polymerase begin the transcription process for filoviruses?
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What happens when little or no free NP protein is present during the initial infection?
What happens when little or no free NP protein is present during the initial infection?
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What is added to the RNA during the transcription process to resemble cellular mRNAs?
What is added to the RNA during the transcription process to resemble cellular mRNAs?
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In the context of filovirus replication, when are high levels of NP important?
In the context of filovirus replication, when are high levels of NP important?
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Which proteins are associated with the genomic RNA and/or nucleocapsid in filoviruses?
Which proteins are associated with the genomic RNA and/or nucleocapsid in filoviruses?
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What defines the transcription process of filoviruses compared to other '-‘ sense RNA viruses?
What defines the transcription process of filoviruses compared to other '-‘ sense RNA viruses?
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What happens to RNA polymerase after it transcribes a short sequence during initial infection?
What happens to RNA polymerase after it transcribes a short sequence during initial infection?
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What are the two genera of filoviruses?
What are the two genera of filoviruses?
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What is the most probable source of transmission of filoviruses to primates?
What is the most probable source of transmission of filoviruses to primates?
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What is the typical genome structure of filoviruses?
What is the typical genome structure of filoviruses?
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Which of the following is a characteristic of filovirus infections among humans?
Which of the following is a characteristic of filovirus infections among humans?
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Which symptom is NOT associated with infections caused by Marburg and Ebola viruses?
Which symptom is NOT associated with infections caused by Marburg and Ebola viruses?
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How many genes are contained within filovirus genomes?
How many genes are contained within filovirus genomes?
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What is the mortality rate that can be associated with filovirus infections?
What is the mortality rate that can be associated with filovirus infections?
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Which of the following proteins gets cleaved into GP1 and GP2 in filoviruses?
Which of the following proteins gets cleaved into GP1 and GP2 in filoviruses?
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What effect does the addition of an extra 'A' residue by RNA polymerase have on the derived protein?
What effect does the addition of an extra 'A' residue by RNA polymerase have on the derived protein?
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What type of immune response is commonly triggered by filovirus infections?
What type of immune response is commonly triggered by filovirus infections?
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Which of the following proteins is synthesized as a precursor and undergoes cleavage during processing?
Which of the following proteins is synthesized as a precursor and undergoes cleavage during processing?
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Which receptor is specifically associated with liver cells and involved in glycoprotein internalization?
Which receptor is specifically associated with liver cells and involved in glycoprotein internalization?
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Which of the following statements about the Ebola virus is true?
Which of the following statements about the Ebola virus is true?
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Which protein is considered the most common product of Ebolavirus gene editing?
Which protein is considered the most common product of Ebolavirus gene editing?
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What role does cellular furin protease play in the processing of GP?
What role does cellular furin protease play in the processing of GP?
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What is the primary function of filovirus GP proteins?
What is the primary function of filovirus GP proteins?
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What modification occurs to GP during its processing in the ER?
What modification occurs to GP during its processing in the ER?
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What is a possible outcome of the RNA polymerase 'stuttering' over a stretch of 'U's?
What is a possible outcome of the RNA polymerase 'stuttering' over a stretch of 'U's?
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Which statement about filovirus pseudotypes is true?
Which statement about filovirus pseudotypes is true?
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What type of bond holds GP1 and GP2 together after cleavage?
What type of bond holds GP1 and GP2 together after cleavage?
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What is the diameter range of influenza viruses?
What is the diameter range of influenza viruses?
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Which surface glycoproteins are used to differentiate subtypes of influenza viruses?
Which surface glycoproteins are used to differentiate subtypes of influenza viruses?
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Which genera are included in the Orthomyxoviridae family besides influenza?
Which genera are included in the Orthomyxoviridae family besides influenza?
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Which population is most likely to experience severe symptoms from influenza virus infections?
Which population is most likely to experience severe symptoms from influenza virus infections?
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What annual impact do influenza A viruses typically have?
What annual impact do influenza A viruses typically have?
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How many deaths does influenza cause annually in North America?
How many deaths does influenza cause annually in North America?
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What compounding issue can arise from influenza virus infections in the respiratory tract?
What compounding issue can arise from influenza virus infections in the respiratory tract?
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What is a potential outcome of emerging avian influenza virus strains?
What is a potential outcome of emerging avian influenza virus strains?
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What mechanism do filoviruses use to enter host cells?
What mechanism do filoviruses use to enter host cells?
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Which statement about sGP is true?
Which statement about sGP is true?
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What is speculated about the function of sGP?
What is speculated about the function of sGP?
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Which proteins are associated with the viral envelope of filoviruses?
Which proteins are associated with the viral envelope of filoviruses?
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In the context of filoviruses, what does GP2 refer to?
In the context of filoviruses, what does GP2 refer to?
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What is the primary role of the viral proteins highlighted in red?
What is the primary role of the viral proteins highlighted in red?
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How might sGP subvert the immune response?
How might sGP subvert the immune response?
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Why might generating pseudotypes be challenging for studying attachment and entry of filoviruses?
Why might generating pseudotypes be challenging for studying attachment and entry of filoviruses?
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Study Notes
Lecture 8 - Negative Strand RNA Viruses
- Filoviruses are characterized by their filamentous, enveloped structure.
- Filovirus diameter is 80 nm, and length can exceed 800 nm.
- Filoviruses have a negative-sense single-stranded RNA genome, approximately 15-19 kb in size.
- Their genome encodes proteins such as nucleocapsid protein (NP), glycoprotein (GP), RNA polymerase cofactor (VP35), polymerase (L), matrix protein (VP40), and VP24
Filoviruses - Structure
- Filoviridae derives from the Latin word "filum" (filament or thread-like).
- These viruses are filamentous and enveloped.
Filoviruses - Disease and Spread
- The first Marburg virus outbreak occurred in Marburg and Frankfurt, Germany in 1967.
- Laboratory workers processing monkey tissues were affected, with a 22% mortality rate (7 deaths out of 32 cases).
- A similar virus, Ebolavirus, emerged independently in Zaire (now the Democratic Republic of Congo) and Sudan in 1976.
- Different Ebolavirus species exist, including Sudan ebolavirus (SEBOV) and Zaire ebolavirus (ZEBOV).
- Marburg and Ebola viruses are sporadically re-emerging viruses causing severe, often fatal disease in Africa.
- A 1994 outbreak originated from Cote d'Ivoire, resulting in the third EBOV species (CIEBOV or Tai Forest).
- Experimental monkeys shipped from the Philippines to Reston, Virginia (USA) in 1990 harbored a non-pathogenic ebolavirus (REBOV).
- Bundibugyo Ebola virus (BEBOV) was discovered in Uganda in 2007.
- The 2014-15 EBOV outbreak was the largest in history, originating in Guinea.
Filoviruses - Genome and Proteins
- Filovirus genomes are linear, negative-sense, single-stranded RNA (~15-19 kb).
- Seven genes transcribed in series from 3' end of the genome using viral RNA polymerase.
- Most genes produce a single mRNA and a single protein (except glycoprotein GP, which is cleaved into multiple proteins).
- Proteins of filoviruses:
- Nucleocapsid protein (NP)
- RNA polymerase cofactor (VP35)
- Matrix protein (VP40)
- Glycoprotein (GP, cleaved into GP1, GP2, or sGP)
- Membrane protein (VP24)
- RNA polymerase (L)
- Glycoproteins are either secreted glycoprotein (sGP) (making up 80%) or GP (20%).
Filoviruses - Replication
- Transcription and replication occurs in the cytoplasm.
- The template for mRNA synthesis is the negative-sense RNA genome.
- The 3' leader contains a promoter for viral RNA polymerase and packaging signal for nucleocapsid assembly.
- During replication, viral RNA polymerase adds a methylated 5' cap and poly(A) tail.
- Genome replication occurs through the synthesis of antigenome RNA.
- Viral RNA polymerase changes its mode to no longer recognize termination/polyA-re-initiation sites.
- Genome RNA is packaged into nucleocapsids during replication.
Filoviruses - RNA Editing
- Ebolavirus uses RNA editing to produce two glycoproteins (sGP and GP) from a single gene.
- sGP (~80%) is a shorter protein without the transmembrane domain located at the C-terminus.
- GP (~20%) has an extra adenine (A) residue.
Filoviruses - Attachment and Entry
- The glycoprotein (GP) is synthesized as a precursor protein and inserted into the endoplasmic reticulum (ER).
- An N-terminal signal sequence is cleaved off during the insertion in ER.
- GP undergoes extensive glycosylation in ER and Golgi and transported to the plasma membrane.
- Cellular furin protease cleaves GP into ectodomain, GP1 (N-terminal) and transmembrane GP2 (C-terminal) proteins.
- GP1 and GP2 are held together by a disulfide bridge (between cysteine residues).
- Filovirus GP mediates binding to multiple cellular receptors.
- Cellular receptors include, asialoglycoprotein receptor, folate receptor–a, integrins, and DC-SIGN.
- Filovirus pseudotypes can be used to study attachment and entry.
Filoviruses - Protein Function
- sGP is released from infected cells and found in serum, acting as a biomarker and potential vaccine/antiviral target.
- sGP's function is unclear; it may substitute as a structural protein or influence replication and infectivity.
- VP40 is the most abundant viral protein and is associated with the viral envelope (located at the cytoplasmic side of the plasma membrane or inner side of the viral envelope).
- VP40, similar to other enveloped virus matrix proteins, bridges envelope glycoproteins to nucleocapsids.
- Expressed VP40 in mammalian cells leads to virus-like particles budding from the plasma membrane.
- Cellular proteins involved in trafficking/sorting of intracellular vesicles (e.g., Nedd4, Tsg101) interact with VP40 in the formation of virions at the plasma membrane.
Influenza Viruses - Structure
- Orthomyxoviridae is derived from Greek 'ortho' (correct/normal) and myxa (mucus).
- The virus is characterized by its enveloped particles, quasi-spherical to filamentous, in shape derived from host membrane via budding.
- Viruses have a diameter of 80-120 nm, and compact helical nucleocapsids.
Influenza Viruses - Types
- Subtypes are distinguished by variations in surface glycoproteins (hemagglutinin (HA) and neuraminidase (NA)).
- Avian influenza viruses (e.g., H5N1, H7N9) can be highly pathogenic, whereas low pathogenic avian influenza viruses have decreased ability to kill chickens in labs.
- Influenza A viruses, most commonly, infect humans. Influenza B viruses mostly infect humans.
- Other genera found in Orthomyxoviridae family, include Thogotovirus and Isavirus.
Influenza Viruses - Disease and Spread
- Influenza A virus infections typically lead to symptoms such as high fever, sore throat, cough headache, and muscular pain, often with secondary bacterial infections in the elderly, infants, and those with chronic illnesses.
- Influenza A viruses cause sporadic pandemics and annual epidemics.
- Avian influenzas are a continual threat to birds, and have potential to infect humans, leading to outbreaks.
Influenza Viruses - Genome
- Influenza viruses have segmented, negative-sense RNA genomes (6-8 different segments).
- Single virions house a complete set of genome fragments.
- The genome size is approximately 10-15 kb.
Influenza Viruses - Genome and Proteins
- Influenza A virus genome has multiple RNA segments (with corresponding proteins).
- Proteins include polymerase complex (PB2, PB1, PA), nucleoprotein (NP), hemagglutinin (HA), neuraminidase (NA), matrix (M1), and M2 ion channels, nuclear export protein (NEP).
Summary
- Virus classifications are used to understand their characteristics, evolution, impact and behaviour.
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Description
This quiz covers the characteristics, structure, and spread of filoviruses, including Marburg and Ebolavirus. Learn about their filamentous, enveloped structure and negative-sense single-stranded RNA genome. Explore the impact of filoviruses on human health through historical outbreaks.
