3 latent and persistant virus

Question 1

what are the characteristics and sequence of an acute viral infection?

Answer 1

rapid onset

only lasts days to a few weeks

there is active replication and then there is generation of a specifica adaptive immune response that will kill the virus and develpe memory.

there is overactive immune response that can cause damage to the host tissue.

Question 2

what makes a chronic infection diffrent from a acute infection?

Answer 2

virus is not cleared

the first robust immune response is held off to prevent immunopathology

the immune response set point is increased to a higher active state. (increased systemic cytokine levels)

Question 3

Two types of viral life styles during chronic infection?

Answer 3

Latent (quiescent) infection

Persistent replication

Question 4

what is the prototype virus for a latent infection?

Answer 4

herpes virus

Question 5

what are the 2 life cycles of a latent infecction?

Answer 5

latent infection

lytic replication

Question 6

what kind of genomic material does herpes have?

is it enveloped?

Answer 6

it has double stranded DNA and it is enveloped.

Question 7

Herpes

what are the shared intial steps that both the lytic and the latent infection share?

Answer 7

– Viral attachment and entry

– Transport of DNA in the nucleus

– Viral DNA circularizes and associates with host nucleosomes

Question 8

herpes

what happens in the latent infection that makes it different from the lytic?

Answer 8

Following initial steps, viral lytic program is halted; instead

• Viral DNA is maintained by the cell as an extra chromosome (episome) – this allows viral genome to survive cellular division
• Very little if any viral genes are expressed
• Few expressed viral proteins help maintain the viral episome and prevent its loss during cellular division

Question 9

what are the advantages and disadvantages of a latent virus infection?

Answer 9

• Advantages

– Stealth – infected cells are invisible to the immune response

– Virus relies on host cell mechanisms to maintain viral genome –(cant makes drugs to eliminate)

• Disadvantages

– Spread to a naïve host is limited (no production of infectious virions)

– Death of a latently infected cell is a dead end for the virus ‐ virus genome is non infectious

Question 10

what cells do latent viruses infect so that they can over come their own death when the cell they infect dies?

what does HIV infect?

what does herpes infect?

Answer 10

they infect long lived cells.

Herpesviruses: neurons, memory T and B cells, hematopoietic stem cells

Human immunodeficiency virus: memory T cells

Question 11

how do latent viruses get transmitted after they are latent?

Answer 11

they are reactivated.

Question 12

what is the prototype virus for a chronic persistant virus infection?

Answer 12

hepititis C virus.

Question 13

what happens to T cells in a chronic persistant virus infection?

Answer 13

T cell exhaustion from the constant stimulation

• T cells upregulate inhibitory receptors that attenuate signaling downstream of T cell receptor (TCR)
• This decreased TCR signaling eventually leads to loss of antiviral functions and death of T cells

it loses IL-production then TNF alpha production and then INF gamma production.

Question 14

what kind of infection is HIV?

Answer 14

it is a combination of a latent and persistant virus infection

Question 15

what kind of cells do HIV infect?

Answer 15

CD4 Tcells

Question 16

what is HAART?

what can it lead to in the blood?

what happens when you discontinue HAART?

Answer 16

Highly active antiretroviral therapy

(HAART) can lead to undetectable virus loads in the blood – but latently infected T cells can persist in the tissues

• Discontinuation of HAART in most cases will allow HIV reactivation and persistent replication, leading to disease

Question 17

what do latent infections do the the immune response? how do they do this?

Answer 17

they keep a low level of immune stimulation, the latent infections reset the base line of the immune response

this increases the systemic cytokine level

and

decreases the activation threshold of the immune system.

– Important implications for

vaccine development

susceptibility to acute viral and bacterial infections • autoimmunity

Question 18

what are some treatemnts for a latent viral infection?

Answer 18

try to target the virus specific machinary

induce reactivation then try to target the lytic

difficult to make vaccine

prophylactic treatment of susceptible hosts with antivirals targeting lytic viral replication is a viable alternative

Question 19

Pathogenesis of persistent virus infection stems from two primary contributions?

Answer 19

1. Tissue and cellular damage associated with virus replication

• – depletion of CD4 T cells in HIV infection
• – hepatocyte death due to replicating hepatitis C virus

2. Tissue damage from excessive immune response and inflammation.

Question 20

in what viruses is chronic inflamation associated with cancer?

Answer 20

in Hep B and C

Question 21

what do thearpies for a chronic virus infection have to target?

Answer 21

Therapies have to target both viral and host processes that lead to disease.

• Viral: therapeutics that specifically target viral replication (i.e. retroviral therapy against HIV)

– Often have to be administered as a combination (to limit the development of resistance) and for a lifetime of infected individual

• Host: since much of tissue damage is induced by the host immune system, mild immunosuppressive therapy can be of benefit

– However, immunosuppression has to be carefully balanced to maintain virus‐specific immune responses

– Therapies that aim to reverse the T cell exhaustion associated with many persistent virus infections – currently under development