AB2, L61: Virus Persistence in Individuals - NEED TO BE EDITED

Given definition, answer w/ term

EDIT

Retrovirus Persistance:

• Mechanism: Viral genome is incorporated into host DNA

  • Viral reverse transcriptase takes viral RNA into DNA. Reverse transcriptase has low fidelity; each time it makes a new virus it introduces many random mutations. Evolutionary pressure gives some mutants advantages

  • Adaptive immune system mounts a very specific response, so mutations allow virus to continue mounting essentially a "new” viral attack

• Example: Lentivuruses (HIV & Equine anemia virus)

Equine infectious anemia

Viral Disease:

• Cause: Lentivirus equinfane

• Transmission: Biting flies

• Clinical Symptoms: Recurrent bouts of symptoms leads to wasting:

  • Acute phase: Fever, jaundice, thrombocytopenia, anemia

  • Followed by seeming recovery where horse mounts adaptive immune response and is asymptomatic

  • Finally chronic phase of recurrent bouts of symptoms that leads to wasting

• Prevention: Vaccine

Immune response in immune privileged sites adapted to suppress rather than kill virus

example: canine distemper virus + measles

initital effect then longterm issues - this is focuses on lognterm issues

• mechanism: copies itself into mRNA, produces protein, leads to virus. No latency or persistency like lentivirus

• Vral eggress = making new infectious virus

• virus picks up random mutation in M protein (no longer expresses M protein). there’s still buildup of viral glycoproteins, but they can no longer form nucleocapsid

• this leads to fusion of infected cell and uninfected cell. this fuse cell will continue to produce glycoproteins

• this forms synctica (neurons fused together)

• in neurons, immune system doesn’t wipe them out

• This leads to dementia - no cure or treatment

Canine distemper

Viral Disease:

• Cause: Paramyxoviridae virus

• Transmission:

• Clinical Symptoms:

  • Acute respiratory infection in the lymph node leads to

  • Viremia in various organs, and crosses over to the CNS, which results in either acute encephalitis or chronic infection (“old dog encephalitis)

• Prevention: Vaccinate

Hiding in immune privileged sites

Virus Persistance: Skin

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• Cornified layer = surface

• Infection w/ papilloma from damaged to skin where virus is able to get to basal layers

• virus evolved so it doesn’t produce new virus when they’re in basal cells

• then, virus moves up through skin layer

• then, near the top, transcriptional environment is correct for virus and it triggers replication. these cornified cells do not have blood supply, so immune system is not triggered

Tolerance

Virus Persistance:

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• hot is unable to recognize virus, even though it’s replicating

• Example: bovine viral diarrhea virus

• virus replicates quickly and spreads rapidly. there’s 2 styles: classical acute virus that spreads and is cleared, and animal is immune. second, congenital infection.

  • Within the first 80 days of cow being pregnant → abortion

  • Between 80-125 days of pregnancy: Calf develops tolerance to virus (considers virus to be self)

  • Greater than 125 days: Calf able to clear virus

• Calf born without ability to mount immune response to BVDV

• Virus will continue replicating throughout animal’s life

• Symptoms:

  • Profuse watery diarrhea

  • Chronic weight los

  • Ulcers in the mouth, gums, dental pad, and muzzle

  • Excessive salivation and nasal discharge

• Host is a super spreader

Latency

Virus Persistance:

• Example: Herpesviruses and varicella zoster virus

• Mechanism:

  • Encode 100s of genes, most of which are dedicated to changing the cellular environment they’re in and changing the immune response

  • There’s 2 main pathways: :

    • Acute: early genes, late genes, new virus

    • Latent: Early genes are suppressed, leading to latent infection that is reactivated and leads to acute

• You never recover from herpesvirus

List the 3 subfamilies of herpesviruses

Alpha herpesvirus

Assosicated with latent infection of the nervous system

Example: Varicella zoster (chickenpox), important veterinary because they tend to lead to some disease

Beta herpesvirus

Gamma herpesviruses

Associated with lymphoproliferative disorders

slower replciating, affect immune cells

Latency is different (alpha go latent in neruons which are terminally differentiated)

• in gamma, immune cells divide meaning virus will get diluted out

• to mantain its genome in rapidly dividing cells, it takes advantage of cell development

• virus triggers pathway to differentiate into memory b cell, where it can hide out for a long. it only produces a subset of viral proteins

OHV-2 Pathogenesis (sheep)

• healthy sheep and diseased sheep look the same. infects B cells, drives B cell differentiation and maintaining itself longterm

• occasioanlly can jump into cattle, leading to extreme symptoms. trying to do the same thing, but signaling goes wrong. drives t cells to differentiate, then looses control, and leads to lymhoma

Immunosuppression

-Eample : Immunodeficiency virus

• Mechanism: Targets CD4+ T helper cells (critical to adaptive immune response)

• rapid replication, host abel to get it under control, clinical latency where host seems helathy althugh virus is latent and still reproducing, then virus exhausts t cells and host eliminated CD4 cells, then virus takes off, then animal typically dies of opportunisitic infection

Defective replication

Virus Persistance:

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Immunological tolerance

Virus Persistance:

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Viral Immune Evasion Within Host:

• Mechanism:

Viral Modulation Within Host:

• Mechanism: