Virology Basics - Structure, Function, & Host Response

Question 1

Eclipse Period of a one-step growth curve

Answer 1

The period of time between 0 and 12 hours after virus adsorption; represents the time period when virus particles have broken down after penetrating cells, releasing their genomes; no infectious virus is detectable inside or outside of the cell

Question 2

Latent period of a one-step growth curve

Answer 2

The time it takes from the initiation of infection to the release of new infectious virus particles from the cell

Question 3

(+) ssRNA viruses (5 examples)

Answer 3

“Ribosome ready” - can be directly translated on the (+) mRNA strand by host ribosomes

RdRp are packaged within the virion to replicate the viral genome

Coronavirus
Polio
Hepatitis A
West Nile
Hepatitis C

Question 4

(-) ssRNA viruses (5 examples)

Answer 4

RdRp contained within the virion must copy (-) RNA into (+) RNA prior to becoming “ribosome ready” for translation; RdRp can also replicate the viral genome

Ebola
Measles
Influenza
Mumps
Rabies

Question 5

dsRNA viruses (1 example)

Answer 5

RdRp contained within the virion acts on the (-) RNA to make “ribosome ready” (+) mRNA

Rotavirus

Question 6

Retroviruses

Answer 6

(+) stranded RNA virus with a DNA intermediate

(+) ssRNA is copied into dsDNA via reverse transcriptase; viral dsRNA then integrates into the host cell DNA where it is transcribed into mRNA by host RNA polymerase II

Reverse transcriptase comes fully assembled within the viral particle

Question 7

Tissue tropism

Answer 7

The propensity of a virus to infect certain tissues and not other, determined by viral access to the tissue, receptors required for virus binding and try, expression of host genes required for virus replication, etc.

Ex: enterotropic viruses replicate in the gut, neurotropic viruses replicate in the nervous system

Question 8

Virulence

Answer 8

The capacity of a virus to cause disease, determined by genes that affect the virus’ ability to replicate, modify host defense mechanisms, cause direct toxicity to cells, etc.

Question 9

Acute local viral disease

Answer 9

Usually caused by infections of epithelial cells of mucosal surfaces; virus replication & shedding occurs primarily within the original site of infection

Usually involves viruses that mutate rapidly and have many different serotypes; therefore, re-infection is common

Characterized by short incubation periods (1-2 days) and strong IgA immune response

Question 10

Acute systemic viral disease

Answer 10

Primary infection occurs in epithelium but virus breaches local barriers (basement membrane, connective tissue, etc.) to cross into hematological / lymphatic system; viremia results in secondary replication at various sites, often lymphoid organs, lung, liver

Incubation period is usually 10-21 days; shedding may take place from the epithelium as well as multiple systemic sites

Infection results in lifelong immunity mediated by secretory IgA and serum IgG

Question 11

Persistent viral infection

Answer 11

Viral infections that continue to produce new viral particles over a long period of time

Ex: Hepatitis B

Question 12

Latent (reactivating) infection

Answer 12

Viral infections in which periods of little gene transcription and disease may be interrupted by re-initiation of transcription and replication to produce new virus particles

Question 13

Mechanisms of virus-induced immunopathology (6)

Answer 13

Antigen-antibody complex disease mediated by complement

Cell-mediated responses and destruction - innocent bystander effect

Virus-induced inflammation - acute phase response

Virus induced immune suppression

Antibody dependent enhancement of infection

Virus-induced autoimmunity

Question 14

Viral transmission - enveloped vs. non-enveloped

Answer 14

Enveloped viruses are fragile and sensitive to environmental stresses; they are most often transmitted by close contact

Non-enveloped viruses can sustain drying, low pH, detergents, and high temperatures; they are often transmitted via respiratory and oral/fecal routes, or fomites

Question 15

Transforming viral infections

Answer 15

Viruses that contribute to tumorigenesis via activation of oncogenes, inactivation of tumor suppressors, or DNA breakage; may be mediated by either retroviruses or non-retroviruses

Some persistent viral infections may cause ongoing inflammation and so contribute to tumorigenesis

Question 16

3 outcomes of viral infection

Answer 16

1. Abortive infection - failed infection, no virus produced, no effects on cell
2. Lytic infection - results in production of virus and death of the infected cell
3. Persistent infection - chronic, latent, or transforming

Question 17

Cytopathic effect

Answer 17

Any detectable morphologic changes in the host cell, caused by viral infection; examples include:

Pyknosis
Cytoplasmic vacuolization
Syncytia 
Chromosomal breakage 
Inclusion bodies 
Negri bodies

Question 18

Syncytia

Answer 18

Cell fusion

Question 19

Negri bodies

Answer 19

Protein & RNA in the cytoplasm

Question 20

Permissive vs. Non-permissive

Answer 20

Permissive cells provide the machinery and components required for completion of viral replication; non-permissive cells do not

Question 21

Mechanisms of viral-mediated cell damage

Direct vs. Indirect

Answer 21

Direct - diversion of cell’s energy, shut off of macromolecular synthesis, competition of viral mRNA for cellular ribosomes, etc.

Indirect - integration of the viral genome, induction of mutations in the host genome, inflammation, host immune response, etc.

Question 22

Type I IFNs

Answer 22

a-IFN, B-IFN

Antiviral cytokines transiently produced and secreted by most infected cells within hours of infection

Question 23

Type II IFNs

Answer 23

y-IFN

Produced by T cells and NK cells

Question 24

Role of interferons in production of an anti-viral state

Answer 24

Cells respond to IFNs produced by neighboring infected cells through receptors that signal through Jak/Stat pathways; this affects regulation of transcription factors which control gene expression through interaction with interferon-dependent DNA regulatory elements

Question 25

Intracellular restriction factors (2 examples)

Answer 25

Cellular proteins that can block post-entry steps of certain viral infections

Trim5 blocks retroviruses

APOBEC blocks HIV and HCV - APOBEC incorporates itself into virus particles, damaging the genetic material of the virus; it can be inhibited by HIV protein Vif, which binds APOBEC and targets it for destruction

Question 26

Anti-viral stage

Answer 26

Characterized by altered transcription of IFN-responsive genes resulting in a temporary blockade of cell proliferation (p21), reduced cellular metabolism, increased expression of antigen presenting molecules (MHC-I), induction of apoptosis (procaspases), etc

This is a readiness state - the responding cell need not be infected and the products of IFN-induced genes often depend on viral dsRNA as a co-factor in order to ensure that they are only active under conditions of infection

Question 27

Mediators of the anti-viral state (2)

Answer 27

Protein Kinase R (PKR) - synthesized as an inactive precursor induced by the anti-viral state; activated by dsRNA to phosphorylate and thereby inactivate a cellular translation initiation factor; results in decreased protein synthesis

2’-5’ oligoadenylate synthetase (OAS) - synthesized as an inactive precursor induced by the anti-viral state; activated by dsRNA to stimulate a cellular ribonuclease that degrades RNA

Question 28

Important anti-viral TLRs

Answer 28

TLR3 - recognizes dsRNA
TLR7 - recognizes viral RNA
TLR 9 - recognizes unmethylated CpG

Question 29

Mechanisms of virus evasion of host defenses (7)

Answer 29

Antigenic variation - antigenic drift / shift

Immune tolerance - virus proteins that closely resemble host proteins

Restricted expression of viral genes - “going invisible” to host defenses (latent infection)

Production of viral molecules that act as inhibitors of host defense molecules

Down regulation of host proteins, i.e. MHC-I

Infection of immunoprivileged sites, i.e. Brain

Direct infection of the immune system

Inhibition of apoptosis and cell cycle control

Question 30

Antigenic Drift

Answer 30

Gradual change within the same subtype of a virus that occurs through a slow series of mutations in amino acids constituting the hemagluttinin or neuraminidase surface antigens

Occurs after a viral strain has become established in humans as an adaptation to the development of host antibodies

Question 31

Antigenic shift

Answer 31

Occurs when a virus acquires an entirely novel gene segment, usually from another host species

Gene reassortment occurs when two or more viruses infect a single cell, leading to “swapping” of gene segments between strains and the creation of a new hybrid strain that contains a “novel” surface protein gene from the other species

Ex: Occurs in influenza A - pigs can be infected with swine, bird, and human influenza and therefore serve as a “mixing vessel” for genetic reassortment

Question 32

3 conditions of an influenza pandemic

Answer 32

1. Emergence of a new influenza subtype within a population
2. The virus must infect humans and cause serious illness
3. The virus must have sustained human to human transmission and spread easily among humans

Question 33

H5N1

Answer 33

i.e. “Bird Flu,” a type A influenza primarily affecting domestic poultry in Bangladesh, China, Egypt, India, Indonesia, and Vietnam

Isolated cases of human-human transmission have occurred between family members; not sustained enough to merit designation as a pandemic

Question 34

DNA Viruses (6)

Answer 34

HHAPPPy

Herpes
Hepadna
Adeno
Papova
Parvo
Pox 

All are dsDNA with icosahedral symmetry except for Parvo (ssDNA) and Pox (non-icosahedral)

Question 35

(-) stranded RNA viruses

Answer 35

Bunya
Orthomyxo
Paramyxo
Rhabdo
Arena
Filo

Question 36

(+) stranded RNA viruses

Answer 36

Toga
Flavi
Corona
Retro
Picorna
Calici

Question 37

dsRNA viruses

Answer 37

Reo