GMS6121 Exam 1

Exam 1

The 4 things that viruses lack

(1) Enzymes that produce basic chemical building blocks (2) Enzyme systems that generate usable energy (3) Enzymes/tRNAs/ribosomes that direct protein synthesis (4) Membranes that concentrate and localize key molecules

All viruses have _______ and _______, while only some viruses have ________.

nucleic acids and a capsid; an envelope

A ________ is a complete, infectious virus particle.

virion

Naked capsids are ______ to drying, heat, detergents, and acid.

resistant

Enveloped capsids are ________ to drying, heat, detergents, and acid.

sensitive

General stages of virus infection

1. Adsorption

2. Entry

3. Uncoating

4. Early genes

5. Replication

6. Late genes

7. Assembly

8. Packaging

9. Release

Immunofluorescence

method that uses virus-specific antibodies to detect a specific viral protein, usually in a tissue section biopsy or cells from fluid

ELISA (enzyme-linked immunosorbent assay)

method that uses virus-specific antibodies to detect virus particles or secreted viral proteins in fluid

Electron microscopy

method used to detect viral particles in lesions

Cytopathic effects include:

-Cell lysis -Rounding (or other morphological changes) -Syncytia -Inclusion bodies

Transformed cells display one or more of these changes:

-Loss of anchorage dependence -Loss of contact inhibition -Colony formation -Immortalization -Tumor formation in immunocompromised mice

Why do virus preps have such low infectivity?

-Not all virus particles are intact -Virus particles can contain defective genomes -Virus particles can be empty -Cells have antiviral defense mechanisms

Serology

the diagnostic detection of antibodies in serum, to measure the immune response to viral infection

Antibodies to virus proteins are generated by _____ in response to infection.

B cells

Pathogenesis

the process by which one organism causes disease in another

The majority of viral infections are __________.

subclinical

Two components of viral disease:

-Effects of virus replication on the host -Effects of host response on virus and the host

Tamiflu is a ________ inhibitor.

neuraminidase

An example of a live attenuated vaccine is:

polio vaccine.

An example of a subunit vaccine is:

Hep B vaccine

The ____________ is the most common route of viral entry.

respiratory tract

Mechanical barriers to infection in the respiratory tract include:

-Mucus traps viruses -ciliary action propels viruses out of the lungs -sneezing -coughing

Cellular barriers to infection in the respiratory tract include:

macrophages in alveoli

Humoral barriers to infection in the respiratory tract include:

IgA

Virus infection of cultured cells can be observed by cytopathic effect (CPE), which most frequently manifests as:

cell lysis

The most common method to quantify virus infection in a laboratory is by:

plaque assay

Hemaglutination assay can be used to quantify viruses that are able to bind to:

red blood cells

The number of plaques detected in one well of a plaque assay is a reflection of the amount of ________ and the amount of ________.

virus in the sample; sample dilution

Serology is an indirect method of virus detection because it measures the amount of _____ in a patient's serum.

antibody

Barriers to viral infection of the GI tract

-acid pH of the stomach -bile detergents -mucosal IgA -thick layer of mucus

An infection where the virus can spread to many different organs in the body

systemic infection

Viral induction of pyrogenic cytokines that stimulate fever, antibody-dependent enhancement of viral infection, and generation of immune complexes during chronic infections are examples of _______.

immunopathology

Viruses in nature are _____ genetically diverse than viruses in the laboratory.

more

Reassortment can only occur for which class of virus?

Viruses with segmented genomes

Why do RNA viruses have a higher rate of mutation than DNA viruses?

-Their polymerases lack proof-reading activity -They have low-fidelity polymerases. -Their genomes are much smaller so the replication rate is much quicker.

What are the mechanisms by which picornaviruses can release their genomes into the cytoplasm of target cells?

Formation of pores in the membrane AND dissociation of the virion in acidic endosomes following endocytosis

What factor recruits host translation initiation factors to the 5' end of picornavirus genomes to initiate protein production?

internal ribosome entry site (IRES)

Which poliovirus vaccine is in common use in the US today?

IPV (inactivated polio vaccine)

What recruits host translation initiation factors to the 5' end of the calicivirus genomes?

The viral VPg protein

How are norovirus structural proteins synthesized?

They are translated from a subgenomic mRNA produced late in the replication cycle.

Astroviruses cause what type of disease outcome?

Gastroenteritis

Which classes of viruses have evolved to infect the GI tract?

-Reoviruses -Noroviruses -Coronaviruses

________ are a major portal for pathogen entry into the GI tract.

M cells

Barriers to infection of the urogenital tract

-mucus -low pH

Examples of viruses that can spread from the urogenital tract

HIV, HSV

Example of a localized viral infection of the eye

conjunctivitis

Example of a viral infection that can disseminate from the eye

HSV-1

Outcomes of infection at the single-cell level

-Cell death -Abortive infection -Persistent infection -Transformation

Abortive infection

A virus can inter a host cell but cannot generate infectious progeny

Cell death from viral infection may result from:

-Diversion of cell's energy -Shutoff of host macromolecular synthesis -Competition of viral mRNAs for cellular ribosomes -Competition for cellular transcription factors

Cell lysis in vivo results in release of ________.

pyrogens

Example of an abortive infection

HPV

Persistent infection

No cell death and cells are not altered significantly in their growth habits

Three types of persistent infections

-Chronic infections -Latent infections -Recurrent infections

Transformation

Virus infects and genetically alters a cell; result is abnormal cell growth

Types of abnormal cell growth

-loss of contact inhibition -loss of polarization -immortalization -disruption of cell cytoskeleton

Immortalization

Cells replicate out of control

___________ encode an oncogene that blocks a cellular tumor suppressor gene.

Papillomaviruses

________ integrate into host genomes and can disrupt cell cycle regulatory genes.

Retroviruses

What are the determinants of viral tropism?

-Accessibility of the permissive cell -Presence of appropriate cell surface receptors -Presence of intracellular host factors required for virus replication -Absence of suppressive antiviral mediators

________ release of virus facilitates virus dispersal.

Apical

_________ release of virus facilitates dissemination, providing access to underlying tissue.

Basolateral

Routes of dissemination

-Hematogenous spread -Neural spread

________ spread is the most effective, rapid, and common means of dissemination

Hematogenous

Primary viremia

virus replicates at its primary site of infection

Secondary viremia

Virus is disseminated from primary site, through tissue, and then accesses the blood again.

The amount of virus in the blood is higher in _______ viremia than in _______ viremia.

secondary; primary

Passive viremia

results from virus introduced into blood without replication; virus does not replicate until it reaches target organ

Active viremia

Virus replication occurs preceding viremic phase

Cell-associated hematogeneous spread

-May replicate in migratory cells, such as dendritic cells and lymphocytes, which move around the body via the bloodstream -May adhere to RBCs or platelets without replicating

Neural spread

Certain viruses spread from primary site of infection by entering local nerve endings

Viruses can encode proteins that suppress IFN response by:

-blocking IFN induction -blocking IFN signaling -blocking IFN-induced antiviral proteins

Types of immunopathology

-Viral induction of flu-like symptoms -Over-stimulation of the innate immune response -Antibody-dependent enhancement of infection (ADE) -Immunopathology via generation of immune complexes

Immune complexes

virions bound by specific antibody

What are the processes by which viruses naturally acquire genetic changes?

-Recombination -Reassortment

For induced mutation, the goal is __________.

single nucleotide changes

Examples of chemical mutagens used in the lab

-hydroxylamine -nitrous acid -alkylating agents

Example of physical means of inducing mutation

UV crosslinking

Forward genetics identifies:

the gene of interest

Reverse genetics identifies:

the function of the gene of interest

Picornaviruses are ________ viruses with ______-sense RNA genomes.

nonenveloped; positive

Picornavirus translation is initiated by _________.

internal ribosome entry site (IRES)

Examples of picornaviruses

-Poliovirus -Hepatitis A viris -Foot-and-mouth disease virus (FMDV) -Rhinoviruses

Picornavirus genome codes for a ___________.

Polyprotein

Picornaviruses have a(n) ________ structure comprised of ______ subunits.

icosohedral; 60

The basic building block of a capsid is _________.

protomer

Poliovirus uses the receptor ___________.

CD155 (Pvr)

Most rhinoviruses use the receptor __________.

ICAM-1

For poliovirus and rhinovirus, the receptor binding site is in/on _________.

the canyon

For apthoviruses and cardioviruses, the receptor binding site is in/on _________.

surface loops

What are the two mechanisms for genome release from the capsid of picornaviruses?

-pH-dependent dissociation -formation of a pore in the cell membrane

pH-dependent dissociation

Receptor-mediated endocytosis followed by uncoating triggered by acidification in endosomes

________ releases its genome from the capsid via formation of a pore in the cell membrane.

Poliovirus

_________ and _________ release their genomes from the capsid via pH-dependent dissociation.

FMDV and rhinovirus

______ protein acts as a plug in the picornavirus virion.

VP3

1-2 hpi of picornaviruses involves a sharp decrease in __________.

cellular protein synthesis

2.5-3 hpi with picornaviruses, _________ accumulate.

viral proteins

3.4 hpi with picornaviruses involves _______ of _______.

permeabilization of the plasma membrane

4-6 hpi with picornaviruses involves _________ in cytoplasm.

virus assembly

6-10 hpi with picornaviruses involves ______ and _________.

cell lysis and release of virus particles