intro to virology

what is the standard definition for viruses?
small obligate intracellular pathogens, used to be called “filterable agents”
are viruses visible by light microscopy?
you only see them under electron microscopy
where can viruses replicate? why?
viruses are only able to replicate only in living cells. they have no subcellular organelles and rely in host protein synth machinery.
can you cx a virus?
only if you innoculate them into cells in a cx
do viruses divide? what are virions?
progeny virions are assembled, so the virus itself doesn’t divide. virions: another term for a viral particle
what are viruses made of? what sorts of genomes can they have?
nucleic acid enclosed in a protein coat. their genome can be DNA or RNA, but not both
what is found in the core of the virus?
the genome and the associated enzymes. some viruses have a polymerase included
what shapes can the protein coat of viruses take?
virus protein coats, called capsids can be helical, (cylinder and the DNA or RNA is inserted into the middle) or icosahedral, (20 sided figure; has a lot of stability and strength)
what is the nucleocapsid? what are viruses w/out an envelope called? what else would be found in an enveloped virus?
a term used for the capsid when surrounded by an envelope, referring to the core and the capsid together. viruses w/out an envelope are called naked viruses, (only have nucleocapsid, and no envelope). glycoproteins would be found in the membrane, in addition to the nucleocapsid
what are the main functions of the viral capsids?
the main function of viral capsids is to protect the genome, but they are also involved in entry or uncoating.
what is uncoating?
uncoating is the process where the genome is released from the capsid, which is necessary for the virus in order to replicate and transcribe its genome to make messenger RNA – some capsid proteins are involved in this.
how are the viral capsids involved in assembly?
viral proteins usually self assemble and at some point and the genome is inserted into the middle, capsid proteins can package viral enzymes if necessary
what is the viral envelope?
a host derived lipid bilayer, (from the plasma membrane or internal membranes)
what are the two viral encoded proteins that are present in all envelope viruses?
matrix proteins that are involved in assembly, (form a bridge between the capsid and the part of the membrane that has viral proteins in it to make a complete viral particle), and surface glycoproteins, whose main function is cell attachment/virus-cell fusion. they can also bind host neutralizing (protective) antibodies
what kind of antibody response can be made against surface glycoproteins?
neutralizing antibody response, (specific kind of antibody response that can actually prevent an infection – if the virus cannot attach to the cell, it can’t infect it), there are other antibodies can still permit virus to host cell attachment
how are viruses classified?
type of genome (DNA RNA), capsid morphology (helical vs icosahedral), and naked vs enveloped
what characterizes DNA viruses?
their genome can persist over time and integrate into the host chromosome as it resides in the nucleus. it can use host polymerases and interact with host transcription factors
what characterizes RNA viruses?
their genome is more labile, it remains in the cytoplasm and RNA viruses have to encode their own polymerases. they are also more prone to mutations
what are retroviruses? what is a clinical consequence of their type of replication?
RNA viruses that can make a DNA copy of their genome during replication called cDNA. this can cause a latent infection.
what is a clinical consequence of RNA viruses?
there is a lot of variance due to high mutation rate, seen in HIV and Hep C
what are some characteristics of naked icosahedral viruses? can they exist outside of a host? how are they released?
these cause many vases of gastroenteritis, b/c the capsid provides protection for the genome from drying out, pH/temp extremes, detergents, etc. since they don’t have envelopes, they are released via cell lysis
what are clinical consequences of naked icosahedral viruses? are these cytopathic?
these can transmit easily via fomites, b/c they don’t dry out like enveloped viruses. stools are one way they can be spread. naked icosahedral viruses can be cytopathic and are usually more pathogenic than enveloped viruses
what are some characteristics of enveloped viruses? can they exist outside a host? how are they released?
destroying the envelope will negate their infectivity, (any sort of drying will make them inactive). they are acid and heat labile and organic solvents will damage their infectivity due to damage to the envelope. they are released from cells via budding (how they gain their envelope) or possibly cell lysis.
what are the clinical implications of enveloped viruses? do they have to kill infected cells to spread? how well do they stand the GI?
they are transmitted through respiratory droplets and secretions, (coughing, sneezing, aerosols, blood, organ transplants). enveloped viruses don’t have to kill infected cells to spread. they tend to not survive in the GI tract.
what is the first step in the replication cycle?
attachment, where specific binding between a glycoprotein on the viral surface binds the receptor of the host cell. with enveloped viruses, this involves surface proteins and with naked viruses, this involves capsid proteins.
what is trophism? what determines this?
the ability of a virus to infect a particular type of cell, attachment is not the only determinant of this, but it is the most important and first component of this determination
what kinds of cellular receptors on the host cell interact with viruses?
proteins or carbohydrates on glycoproteins or glycolipids on the host cell surface that can have physiological roles intracellularly including cell-cell interaction and hormone, cytokine, or complement involvement
what is the next step in viral replication after attachment?
entry and uncoating. the virus can enter through receptor-mediated entry w/an endosome or directly through the plasma membrane. uncoating is the release of the genome in to the cell, (DNA virus genome -> host nucleus, RNA virus genome -> host cytoplasm)
how does entry directly through the host plasma membrane occur with enveloped and naked viruses?
enveloped viruses’ membranes fuse with that of the host cell and naked viruses can create a channel through the membrane via hydrophobic interactions
can receptor mediated endocytosis occur with both enveloped and naked viruses?
yes, and this is the most common route of entry for viruses, (naked viruses tend to favor this mode of entry)
what are the two variations of receptor-mediated endocytosis?
clathrin mediated and caveolae dependent pathways
how does the clatrin mediated pathway work in viral receptor-mediated endocytosis?
clathrin coated pits envelope the virus into an endosome which is taken inside the cell. the endosome must be acidified for the fusion proteins to be activated and thus allow the virus to leave
how does the caveolae-dependent mediated pathway work in viral receptor-mediated endocytosis?
the host membrane contains invaginations called caveolae that contain a lipid-raft associated proteins called caveolin. the virus is enveloped in a vesicle called a caveosome wich is then released into the cytosol. viruses have to be able to fuse at a neutral pH to enter this way, (doesn’t need to be acidified)
what must happen in conjunction with viral entry into the cell? how does this process differ between RNA+DNA viruses?
the capsid has to be able to dissociate so the genome can get loose in the cell. w/RNA viruses, uncoating and penetration will occur at the same time with the genome being released into the cytoplasm. w/DNA viruses, the caspid stays intact until it reaches the nuclear membrane and then the genome enters via a nuclear pore
how does uncoating occur with naked viruses (once in endosome)?
there is a conformational change in the capsid proteins and lysis or permeability (channel formation), of the endosomal membrane occurs. triggers for this include binding of a receptor, change in pH, and proteolytic degradation
how do viruses take over host cell protein synthesis machinery?
the host cell is directed to start making viral proteins though initiation of viral mRNA transcription, replication of the viral genome, and shutting down host protein synthesis.
what do the early viral transcripts do?
the early viral transcripts encode regulatory enzymes & proteins that control transcription of the viral mRNA and replication of the viral genome
what do the late viral transcripts do?
encode viral structural proteins, aren’t needed until late in the cycle
where does DNA virus transcription/replication occur? what is the genome a template for? is it infectious? what host genetic machinery does the virus use?
DNA virus transcription/replication occurs in the nucleus except for pox viruses. the genome is a template for mRNA and is infectious, (if you take ONLY the genome of the host virus and place it into a cell, the cell can make the whole viral particle). the virus uses host cell DNA-dependent RNA polymerase, (but some more complex DNA viruses can encode their own polymerase)
what does the positive strand RNA virus genome function as? what does the virus encode? where does the RNA polymerase come from?
a positive strand RNA virus’s genome is by definition the mRNA, (-strand RNA is complementary). the genome is thus translated as a polyprotein, which is then cleaved by a virus-produced protease. the virus has to encode its own RNA-dependent RNA polymerase which then transcribes – strand RNA which is the template for mRNA as well as the + strand RNA virus genome. the genome is infectious
what do – strand RNA viruses need packaged with them as opposed to + strand RNA viruses? what does their genome function as?
– strand RNA viruses need an RNA-dependent RNA polymerase to be packaged with them. the – strand RNA genome functions as a template for mRNA and it encodes a + strand copy/template of the genome which is then encoded back into – strand RNA genomes for replication
how do double stranded RNA viruses replicate?
double stranded RNA viruses are kind of combinations of +/- strand RNA viruses. the genome is segmented, with different viral proteins encoded on different segments of RNA. the virus encodes a RNA-dependent RNA polymerase which is a core protein. the positive strand RNA transcripts are mRNAs and the template for negative strand synthesis and vice versa
how do retroviruses work?
retroviruses are RNA viruses that make a DNA copy of their genome. their positive strand RNA geome is transcribed into DNA in the cytoplasm by reverse transcriptase, (by RNA-dependent DNA polymerase that is a core enzyme). the cDNA travels to the nucleus, where it integrates into host chromosomes, transcription of which produces mRNA and genomic RNA
what is the definition of infectious genomes?
if you put the genome itself into a cell and you can make a viral particle it is infectious, DNA (except pox) and + strand RNA viruses fall into this category, (negative strand RNA viruses have to bring their own RNA-dependent RNA polymerase)
what are non-infectious genomes?
negative strand RNA viruses, double stranded RNA viruses and retroviruses all fall into this category, (these are where the polymerase is a core enzyme)
how do + strand RNA viruses differ from most other viruses in terms of transcription of viral transcripts?
the entire mRNA genome is translated as a poly peptide that will be cleaved into individual viral proteins
what are the 3 ways viruses other than + strand mRNA translate their mRNA?
subgenomic mRNA (smaller pieces), either encode a single viral protein, encode a poly protein that is then cleaved into multiple proteins, or encodes proteins w/overlapping reading frames
how are capsids assembled?
capsids self-assemble
how are naked viruses/virions released?
cell lysis
how are enveloped viruses released? from where?
budding or lysis. they can bud from the plasma membrane ER, golgi, nuclear membrane, all via exocytosis. budding has to occur at a place in the membrane where viral proteins have been incorporated