Intro to viruses Flashcards

Question

Clathrin-mediated vs Caveolin-mediated ENDOcytosis

Answer 1

_Clathrin-mediated:_ 1. **pH-dependent entry into an endosome** 2. virus gets internalized from a region of the plasma membrane that contains a protein called clathrin, forming a “clathrin-coated pit”. The virus becomes enclosed within a vesicle called an endosome, which subsequently fuses with a lysosome. During this process, the pH of the endosome becomes more acidic. Some viral fusion proteins require exposure to either an acidic pH or lysosomal proteases to become activated so that they can mediate fusion between the viral envelop & the membrane of the endosome. _Caveolin-mediated:_ 1. **pH independent entry** 2. In caveolin-mediated endocytosis, virus becomes internalized at membrane invaginations that contain a protein called caveolin. These invaginations occur at a region in the plasma membrane that has a high density of relatively detergent-resistant lipids called lipid rafts. The vesicles containing virus fuse with other caveolin-containing vesicles forming a caveosome – these vesicles do not become acidified. Virus can be transported to other regions of the cell (such as the ER) before the genome is released into the cytosol.

Answer 2

1. Viral capsid proteins form a pore through the endosomal membrane 2. Viral capsid proteins lyse the endosomal membrane 3. Conformational change in capsid proteins * Expose a hydrophobic region (make a pore) * Dissociate to release the genome (uncoating) 4. Potential triggers for conformational change * Acidic pH * Proteolytic activity * Receptor binding

Answer 3

_Objectives_: * get rid of the capsid * RNA ==\> cytoplasm * uncoating coincides with entr * DNA ==\> nucleus _Triggers for uncoating include:_ 1. binding to a receptor 2. change in pH 3. proteolytic degradation On image: ![]() 1. Step 1 involves **attachment of the fiber to the primary receptor**, which is on most cell types and for most HAdV types is either CAR or CD46. 2. This is followed by **clathrin-mediated endocytosis** in step 2, which is facilitated by the penton base interaction with αv integrins. 3. The virion begins to dissociate in the low pH environment of the early endosome (step 3), 4. and releases the vertex proteins including pVI in the early or late endosome (step 4). Protein pVI has been implicated in disruption of the endosomal membrane, allowing the virion to escape from the endosome. 5. The partially disassembled virion is transported by the microtubule motor dynein along microtubules to the nuclear pore complex (step 5). 6. At the nuclear pore the viral DNA is imported into the nucleus (step 6).

Answer 4

1. Control transcription * make viral mRNA 2. Replicate genome 3. Control protein synthesis * make viral proteins * shut down synthesis of host proteins

Answer 5

1. **Early transcripts:** * encode regulatory enzymes & proteins * control transcription of viral mRNAs * initiate replication of the viral genome * shut down host protein synthesis 2. **Late transcripts:** * encode viral structural proteins

Answer 6

1. Transcription & replication occurs in the nucleus * **exception = pox viruses** 2. Genome = template for mRNA 3. DNA viruses can be single or double stranded 4. Some DNA viruses use cellular polymerases to replicate the genome & transcribe viral mRNA

Answer 7

See image ![]()

Answer 8

1. Genome can function as mRNA * ¡Comparable to the DNA coding strand * ¡translated as a polyprotein, then cleaved 2. Virus encodes an RNA-dependent RNA polymerase 3. Transcription produces (–) strand RNA * ¡template for mRNA * ¡template for genomic RNA

Answer 9

1. Genome can function as mRNA * Comparable to the DNA coding strand * translated as a polyprotein, then cleaved (Coding DNA strand is the one thats identical to transcribed mRNA, sans U residues : U--\>T) 2. Virus encodes an RNA-dependent RNA polymerase 3. Transcription produces (–) strand RNA * template for mRNA * template for genomic RNA

Answer 10

1. Virus encodes an RNA-dependent RNA polymerase * core protein 2. The genome is a template for mRNA * Comparable to the DNA template strand 3. A (+) strand copy of the genome is the template for genomic RNA

Answer 11

1. Genome is segmented * Each segment encodes a protein 2. Virus encodes an RNA-dependent RNA polymerase * Core protein ![]()

Answer 12

1. (+) strand RNA is transcribed into DNA * reverse transcriptase (RNA-dependent DNA polymerase) is a **core enzyme** 2. DNA travels to the nucleus where it integrates into host chromosomes 3. Transcription of DNA produces mRNA and genomic RNA

Answer 13

1. Capsids self assemble * Package genome & core enzymes 2. Naked virions are typically released upon cell lysis 3. Enveloped viruses bud * Matrix proteins determine site of budding * plasma membrane, ER, golgi, nuclear membranes; released via exocytosis * act as a bridge between nucleocapsid & surface glycoproteins **NOTE** – There is evidence that some naked viruses can be released without lysis of the host cell. These viruses appear to induce formation of vesicles that resemble autophagosomes & viral particles are released from these vesicles.

Answer 14

1. **Budding from the cell membrane** 2. ![]() **Budding into the ER** ![]()

Answer 15

1. Disrupt viral structure * ¡Detergent inactivates enveloped viruses 2. Block a virus-specific activity… * ¡Targets include enzymes (polymerases, proteases), attachment proteins (virus specific) * ¡Steps in the replication cycle that are unique to viruses 3. Without interfering with a host cell function * ¡Disrupt host functions ==\> toxicity

Answer 16

1. Productive infection * Progeny virus is produced * Infected cells are permissive for the virus 2. Nonproductive infection * No progeny are produced * Cells are nonpermissive

Answer 17

1. Lytic infection * ¡Destruction (lysis) of the host cell * ¡Produces a cytopathic effect (CPE) 2. Persistent (chronic) infection * ¡Virus buds from host cell without lysing cell * ¡Continual shedding of virus 3. Persistent infections with lytic viruses * ¡Occurs at the tissue or organ level * ¡Some cells in an organ are lysed but not all

Answer 18

_1. Syncytia formation_ * Multinucleated giant cells _2. Cell rounding or vacuolization_ _3. Inclusion bodies_ * New material within host cells detected by histological stains * Sites of viral replication NB: **Type of CPE in a specific host cell helps clinical virologists identify the virus** ![]() ![]() ![]()

Answer 19

1. Abortive * Host cell cannot support viral replication * Viral genome is lost 2. Latent infection * The virus is dormant within the host cell * The viral genome is maintained * Viral transcripts may be detected; few or no viral proteins are expressed * *Immune response does not recognize that the cell is infected* * Occurs in **DNA or retroviruses** * Reactivation of a productive infection is possible Examples: ![]()

Answer 20

1. One or a few viral genes are expressed 2. Immortalized cells _may or may not_ become tumor cells * Transformed cells are immortalized * Immortalized cells over time may pick up mutations that lead to oncogenesis 3. Viral genomes usually integrate into the chromosome in transforming infections 4. Cells are _semi-permissive_ for the virus

Answer 21

1. Inactivate growth-regulatory proteins * p53 * Retinoblastoma gene product (RB) 2. Provide or up-regulate genes involved in cell progression through the cell cycle

Answer 22

1. Uncontrolled cell growth 2. Increased growth rate 3. Alteration of morphology & metabolism * Decreased requirement for serum growth factors * Alterations in cell surface components * Increased metabolic rate 4. Loss of contact inhibition of growth

Answer 23

1. Acute infection * *Localized or disseminated* 2. Chronic infection * Acute infection, then carrier state with persistent shedding of low levels of virus * Latent infection/reactivation of productive infection 3. Transformation – cancer induced by viruses

Answer 24

1. Localized infection * Productive infection at the site of entry * Virus is cleared by the immune response 2. Acute disease * Symptomatic illness 3. Asymptomatic or subclinical infection * **Infected individual can shed virus**

Answer 25

1. Self limiting 2. Site of entry is often mucosal surfaces * Respiratory or gastrointestinal tracts * IgA provides protection 3. Immunity often short-lived 4. **Some cold viruses or viruses causing gastroenteritis**

Answer 26

1. Productive infection at the site of entry * May be asymptomatic 2. Spread via *lymphatics, blood or neurons* 3. Replication at secondary site * Characteristic symptoms 4. Secondary viremia is possible 5. ***_Measles_, _mumps_, _rubella_, _varicella_ (chicken pox)***

Answer 27

1. Virus shedding typically occurs _following initial replication_ * Patient is infectious **before** illness is recognized 2. Incubation period occurs as virus disseminates 3. Nonspecific or flu-like symptoms during dissemination = **prodrome** 4. Symptoms correlate with replication at a secondary site * Illness is recognized 5. **IgG** is important for immunity (usually lifelong)

Answer 28

1. Virus persists over time * Could be productive or nonproductive at the cellular level 2. Productive – viral shedding over time * Cellular level – _host cell is not destroyed_ by the infection * Tissue level – _only a few cells in the population are infected_ at any one time 3. Nonproductive – latency or transformation * Reactivation of a latent virus results in a productive infection * Individual is infectious during reactivation but not during latency * Transformation – cells are altered * Contain viral sequences but do not produce virus, thus individual is not infectious

Answer 29

1. Continual shedding of low levels of virus * patient becomes a carrier * patient is infectious even if asymptomatic * patient may develop clinical disease over time 2. ***Chronic Hepatitis B or C virus; HIV***

Answer 30

1. Initial productive infection occurs upon acquisition of the virus (primary infection) * virus may remain localized or disseminate * may be symptomatic or asymptomatic 2. Latent infection * virus is not replicating (nonproductive infection) * patient is asymptomatic 3. **Reactivation of productive infection** * may be symptomatic or asymptomatic * secondary infections are cleared more rapidly than primary infections * *Herpesviruses*

Answer 31

1. Depends on whether or not the pathogen can overwhelm the immune response 2. Symptoms of disease * Direct result of a virus infecting & killing a cell * Result of the immune response to the virus-infected cells (immune-mediated) 3. Infection can be *subclinical or asymptomatic* * Virus can still be shed and transmitted to a new host

Answer 32

1. Transmission determines site of entry 2. Inoculum size influences severity 3. Tissue tropism determines site of pathology 4. Viral virulence factors * Mechanisms to control host cell protein synthesis * Mechanisms to evade the immune response * Mechanisms to directly damage cells

Answer 33

1. Immune status * Compromised versus non-compromised immunity * Prior immunity 2. General health of the patient * Nutrition 3. Age 4. Genetic background

Answer 34

1. Acute viral infections – treat symptoms * Immune system will eliminate the virus 2. Early initiation of therapy * Viral replication may precede symptoms 3. Chemoprophylaxis * Outbreaks in a confined setting * example – flu outbreak in a nursing home 4. Useful for more chronic infections * *HIV, viral hepatitis* 5. **Current antivirals inhibit _actively_ replicating virus, _not latent infections_**

Answer 35

Information from CDC: 1. Norovirus outbreaks from *contaminated food* are common in food service settings. 2. People infected with norovirus are *very contagious*. * … they shed billions of tiny viral particles i*n their stool and vomit*… 3. Norovirus is *hard to kill* and stays on food, kitchen surfaces, and utensils. It can: * Remain infectious on foods even at freezing temperatures & until heated above 140°F. * Stay on countertops and serving utensils for up to 2 weeks. * Resist many common disinfectants and hand sanitizers. 4. Illness resolves after ~48 hours with no long term consequences

Answer 36

* HIV can cause a _productive, persistent infection in macrophages_; macrophages can shed virus for an extended period of time (days to a couple weeks) * HIV can cause _productive infection in activated T cells_ but l_atent infection in memory T cells_ * The host immune response & anti-retroviral therapy _both provide selection pressure for the generation of quaisispecies_ Each bulleted statement implies what viral property? Virulence/virulent factors, tropism What type of polymerase does HIV encode? Reverse transcriptase (RNA-dependent, DNA polymerase)

Answer 37

1. **Zoster**, but not chickenpox, is an endogenous infection 2. VZV is transmitted primarily via *respiratory droplets*, though manifestation of disease involves *vesicle formation in the skin* 3. Viral entry and uncoating occur at different sites within a cell Each bulleted statement implies what viral property?

Answer 38

Viruses with “infectious nucleic acids” have genomes that are capable of **initiating viral replication** when introduced into a permissive host cell