Viral Lifecycles

Question 1

Characteristic of Acute virus infection: ______onset w/ brief period of sypmtoms—eliminate either host or virus
-ex: influenza, norovirus, rhinovirus

Answer 1

Rapid

Question 2

—generate specific adaptive immune response to clear pathogen—establish memory

Answer 2

Active virus replication

Question 3

Overactive immune response may result in ….

Answer 3

tissue damage (immunopathology)

Question 4

Initial steps simular to acute: virus infects a naïve host, replicates, host mounts immune response w/ some difference (3 differences)

Answer 4

Virus not cleared (for months to a lifetime)
Start with robust immune response—subdued to prevent immunopath by maintain control on virus
Immune response of host is set to a higher activation state overall (increased systemic cytokine levels)
See 2 types of viral life cycles during chronic infection: Latent and persistent

Question 5

Viral lifecycle see______ expression of subset of viral genes, absent lytic replication and infectious virion production

Answer 5

minimal

Question 6

herpes virus is a prototype for a……

has both latent and lytic stages

Answer 6

latent virus infection

Question 7

Viral________ degrades host mRNA

Answer 7

vhs

Question 8

Viral transcription factor localizes to nucleus to initiate viral gene transcription

Answer 8

VP16

Question 9

Viral DNA circularizes and HSV ______transcribed by host RNA II polymerase

Answer 9

alpha genes

Question 10

Some alpha gene products transactivate transcription of

Answer 10

beta genes

Question 11

Some beta gene products are necessary for _______

Answer 11

viral DNA synthesis

Question 12

Viral DNA synthesis triggers expression of

Answer 12

gamma viral genes

Question 13

Gamma gene products are

Answer 13

structual compoents of the virion

Question 14

Viral DNA is packaged into a

Answer 14

capsid

Question 15

Filled viral capsid bud through host membranes to form

Answer 15

a mature virion that exits the cell

Question 16

Initial steps are shared btwn lytic and latent:

–viral attachment and entry→ this consists of

Answer 16

transport of DNA in the nucleus→ viral DNA circularizes and associates with host nucleosomes

Question 17

Viral DNA is MAINTAINED ______(episome) to allow viral genome to survive cellular division

Answer 17

BY CELL as extra chromosome

Question 18

Little if any of the viral genes are expresssed (don’t want to tip off immune system) during

Answer 18

lytic cylce

Question 19

Few expressed viral proteins help maintain the viral episome and prevent…..

Answer 19

its loss during division

Question 20

Advantages of lytic cycle

Answer 20

a. Stealth: few gene expressed to infected cells are invisible to immune system
b. Virus relies on host cell mechanisms to maintain viral genome—very difficult to design therapeutics that specifically target latently infected cells

Question 21

few gene expressed to infected cells are invisible to immune system (advantage of lytic cycle)

Answer 21

Stealth

Question 22

b. Virus relies on _______ to maintain viral genome—very difficult to design therapeutics that specifically target latently infected cells (advantage of lytic cycle)

Answer 22

host cell mechanisms

Question 23

Disadvantages of lytic cycle:

Answer 23

a. Spread to naive host is limited bc no production of virions
b. Death of latently infected cell is a dead end for virus—genome is non infectious

Question 24

Death of latently infected cell is a dead end for virus because:

Answer 24

genome is non infectious

Question 25

Challnge of latent virus: limited transmission to naïve host | Solution:

Answer 25

reactivation-switch from latent→ lytic lifecycle

Question 26

-dangerous for the virus to do this—viral replication during reactivation occurs in the face of a:

Answer 26

robuse and highly virus-spcific adaptive immune response that can eliniate reactivating cell b4 infectious virions are made

Question 27

Challenge: Death of a latently infected cell Solution:

Answer 27

viral latency is established in long lived cells Herpesvirus—neurons, memory T and B cells, hematopoetic stem cells HIV: memory T cells

Question 28

Protype: Hep C virus | Only has a lytic life cycle and can’t shut itself off

Answer 28

Chronic Persistent Virus infection

Question 29

________ continues for duration of chronic virus infection

Answer 29

Lytic replication

Question 30

4. In contrast to latent, during persistent virus replication ________cells are constantly stimulated with high levels of virus antiGs

Answer 30

virus-specific T

Question 31

Constant stimulation prevents development of a robust memory T cell population… leads to immunological phenomenon called _______

Answer 31

T cell exhaustion

Question 32

-T cells upregulate inhibitor receptors that attenuate signaling downstream of TCR

Answer 32

T cell exhaustion

Question 33

T cell exhaustion: | Decreased TCR leads to ......

Answer 33

loss of antivirl fnxs and death of T cell

Question 34

HIV is our prototype for:

Answer 34

Combinations of latent and persistent virus infection

Question 35

If infected CD4 T cell has a memory T cell phenotype, viral replication

Answer 35

becomes very inefficient downstream of viral genome integration

Question 36

__________may lead to undetectable virus loads in the blood—but latent infected T cells persist in tissues

Answer 36

HIGH active antiretroviral therapy (HAART)

Question 37

What happens HIV pts discontinue HAART

Answer 37

Discontinue HAART in most cases will allow HIV reactivation and persistant replication, leading to disease

Question 38

____ is quiescent, little disease is observed

Answer 38

Latent

Question 39

Latent infection: Low level of immune stimulation…latent infections reset baseline of immune response by

Answer 39

increaseing systemic cytokine levels and decrease activation threshold of immune system

Question 40

During a latent infection: Disease is primarily generated by

Answer 40

reactivation and/or expanded viral gene expression

Question 41

Some Epstein Barr virus (gammaherpesvirus) gene products are part of expanded latency associated gene expression have _______ Continuos expression of these, if not limited by host.. can contribute to cancer

Answer 41

oncogenic properties.

Question 42

Overcoming pathogenesis of chronic virus infection: latent infections Elimination of latent infections is challenge as virus relies on

Answer 42

cell machinery to maintain genome—virus specific therapeutic targets are limited if present at all

Question 43

2. One approach to irradicate and/or limit latent infection is to

Answer 43

induce virus reactivation from latency w/ subsequent targeting of lytic virus process (see herpesivirs and HIV blocks for specific therapies) -tricky as all known stimuli induce reactivation only in very small subset of latently infected cells

Question 44

Vaccine devo is difficult bc latency establishment is

Answer 44

extraordinary efficient and often ind of viral replication during initial phase of infection

Question 45

prophylactic tx of susceptible hosts w/ antivirals targeting lytic viral replication is viable alternative because

Answer 45

BC pathogenesis is driven by viral reactivation | -ex: gammaherpevirus-induced sarcomas and lymphomas in context of HIV infection

Question 46

Pathogenesis of Chronic virus infection: persistent Pathogeneis of persistent virus infection stems form two primary contributions:

Answer 46

1. tissues and cellular damage associated w/ virus replication - depletion of CD4 T cells in Hiv infection - hepatocyte death d/t replicating hep C virus 2. Tissue damage associated with inflammation and excessive immune reponse

Question 47

3. Chronic inflammation is associated with

Answer 47

devo of cancer | -hep B and C infection

Question 48

Overcoming pathogenesis of chronic virus infection: persistent infection 1. Therapies need to target both______

Answer 48

viral and host processes that lead to disease

Question 49

Overcoming pathogenesis of chronic virus infection: persistent infection Viral: therapies specifically target ______

Answer 49

``` viral replication (like retroviral therapy against HIV) -often administered as combination (to limit devo of resistance) and for lifetime ```

Question 50

Overcoming pathogenesis of chronic virus infection: persistent infection Host: much of tissue damage induced by ________ --mild immunosuppresive therapies can work -BUT immunosuppresion has to be carefully balanced to maintain _______ -Therapies aim to _____________

Answer 50

host immune system virus-specific immune responses reverse the T cell exhaustion associated w/ persisten viruses