Microbiology: Viruses Flashcards
1
Q
Viral characteristics
A
- Nucleoproteinic entities, oblligate intracellular parasites, replicate directly from their genetic material
- Viral genomes can be ss or ds RNA or DNA, can be linear or circular, can be one or sever pieces, can be plus or minus sense (plus= same polarity as mRNA)
- All viruses contain nucleic acids and proteins, some contain lipid envelope + carbs on outside (proteins+genome compose capsid+core)
- Proteins can be structural (capsid) or nonstructural (nzs)
- Viruses can be helical (form a tubular shell for genome) or cubic (of icosahedron; 20 equilateral triangular faces, and 12 vertices)
2
Q
Cubic viruses
A
- Composed of an icosahedron
- Contains 20 equilateral triangle faces, with 12 vertices
- Capsomers may be pentamers or hexamers. Each pentamer is at the vertices, so there are always 12 pentamers
3
Q
Arboviruses
A
- Arthopod-borne-viruses
- Transmitted by blood sucking arthropod insects
- Many cause encephalitis
4
Q
Life cycle of positive stranded RNA viruses
A
- Absorption: virus proteins binds to specific receptors on the cell surface. Different cell types will display different levels of the receptor and thus the virus will infect different tissue differently
- Penetration and uncoating: Facilitated by receptor-mediated endocytosis of the virus. Once in endosome the viral proteins and their receptors interact to form a pore to extrude the viral genome
- Eclipse: disappearance of viral infectivity early in infection (viral genome inside cell but no progeny made yet). Genetic material sensitive to nucleases at this stage. For poliovirus, the RNA is confined to the cytoplasm
- Maturation and release: Production and assembly of new viruses, which are released when the cell disintegrates (since cell is not left intact, there is no cellular membrane to use as envelope. Thus +stranded RNA viruses are generally naked)
5
Q
Poliovirus replication
A
- Polio genome contains coding for 4 proteins: inhibitors of cellular RNA/protein synthesis, viral RNA polymerase, structural proteins (capsid), protease needed for assembly/maturation
- The viral polymerase and cellular inhibitors are made immediately after uncoating, using cellular ribosomes and viral genome, and before genome replication can commence
- Viral genome replication: begins with parental (+sense) RNA, which is replicated to a template (-sense) strand. When these two complete stands are together, it is called replicative form (RF, has no loose +sense tails)
- The -sense strands are then used to make many copies of new +sense viruses. Many copies are made at once from a single -sense strand, giving the appearance of dsRNA w/ single stranded tails (of +sense strands). This is intermediate form (IF)
- All of this replication is done w/ viral RNA-RNA polymerase. Only +sense strands are incorporated into new viruses (many more +strands made than -strands)
6
Q
+RNA virus polyprotein
A
- The viral genome encodes a single protein (one initiation site) called a polyprotein which contains a protease
- Protease cleaves itself to become activated, then cleaves the polyprotein into the final protein products
- Since there is one initiation site and multiple genes transcribed from it, the RNA is polycistronic
7
Q
Assembly process of poliovirus
A
- First there are VP proteins (VP1,3,0) that form the protomer (one of each VP proteins makes a protomer)
- 5 protomers combine to make a pentamer
- 12 pentamers combine to make a procapsid
- To make a mature capsid, there must be viral RNA progeny and the cleavage of VP0 to VP2 and VP4. This cleavage makes the capsid infectious
- Cellular participation is needed for assembly
8
Q
Influenza virus structure
A
- Contains 2 envelope proteins: HA (hemagglutinin) and NA (neuraminidase)
- HA binds to the cellular receptors and Abs, facilitating absorption and penetration. NA cleaves the cellular receptor (N-acetylneuraminic acid) to allow virus progeny to escape the cell
- Contains matrix (M) protein for structural function (anchors the envelope proteins)
- Contains 8 independent helical nucleocapsid (NC). Each NC has its own (and different) RNA segments needed for replication. Each NC is surrounded by a nucleocapsid protein (NP)
- Each NC contains its own RNA polymerase to initiate primary transcription early on in infection
- All -RNA viruses have helical capsids and are enveloped
9
Q
Replication of -RNA viruses
A
- After receptor mediated endocytosis by HA binding to N-AcNA, lysosome fuses w/ endosome to acidify it. This causes conformational change and eventually fusion of the viral envelope w/ the endosome membrane. This allows the viral genome to enter the cell
- Unlike +RNA viruses which can use their own genome for translation upon entering the cell, -RNA viruses must undergo primary transcription to create +RNA to use for translation
- Since there are 8 NCs, each one must be transcribed on its own into mRNA. Each one of the RNAs encodes a single protein, thus they are all monocistronic (unlike +RNA viruses which are all polycistronic)
- The mRNA of the virus is not a complete copy of the -RNA template since the mRNA ends 15-20 bases from the 5’ end of the template
- The -RNA is transcribed to +RNA by the viral polymerase, which is transcribed again to the -RNA viral progenies (many of these are made)
- Progenies + proteins are packaged together to form mature viruses (they all mature independently), and are released constitutively by budding off from the cell surface (taking the envelope w/ them), without killing the cell
10
Q
Genetic reassortment of the influenza genome
A
-Since influenza has an independently replicated, segmented genome the progenies will often become mixed (when a single cell is infected w/ two or more viruses) and result in genetic reassortment
11
Q
Antigenic drift
A
- Antigenic drift is a slow process during which the influenza virus is changing the antigens on its surface (HA protein)
- This happens via point mutations in the HA gene (usually in 4 distinct areas in the “head” region of the molecule)
- Causes Abs that were once very good at neutralizing the virus to no longer be as effective
- The reason we get yearly flu shots
12
Q
Antigenic shift and flu pandemics
A
- Appearance of new subtypes of influenza causes flu pandemics
- Only influenza A can cause antigenic shift due to the large number of animals that influenza A infects
- Genetic reassortment within a cell infected w/ human and animal subtypes leads to antigenic shift
- Changes the HA and NA molecules on envelope surface (novel proteins) which could only have come from genetic reassortment
- New subtypes appear every 10 years
13
Q
Adenoviruses
A
- Frequent cause of acute upper respiratory tract (URT) infections (often in IC’d patients)
- Naked icosahedral virus w/ dsDNA and proteins
14
Q
Life cycle I of adenovirus
A
- Absorption takes place in 2 stages: first there is binding of fiber protein on virus surface to a variety of cell receptors (including MHC and CAR), then penton base binds to integrins and allows internalization via RME (receptor mediated endocytosis)
- This is followed by rupture of endosome by acidification and breakdown of viral coat (uncoating)
- DNA is injected into nucleus through nuclear pores (DNA must reach nucleus for progeny to be made)
15
Q
Life cycle II of adenovirus
A
- 3 distinct phases: intermediate-early, early and late gene expression
- intermediate-early genes are regulatory growth factors required for subsequent phases and promotion of virus survival and proliferation
- early genes are the proteins required for DNA replication: DNA polymerase, precursor terminal protein (pTP) and DBP (single strand DNA binding protein)
- late genes encode structural proteins
