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Finals: Retroviridae Flashcards

1
Q

How did retrovirus get it’s name?

A

Have important enzymes they encode for reverse transcriptase

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2
Q

Retroviruses infect ___ and ___

A

Animals and humans

Wow, tell me more….

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3
Q

Retroviruses can be the causative agents for what?

A

Cancer
Immunosuppression
Immunodeficiency diseases

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4
Q

T/F: retroviruses may exist as stable components in the host genome

A

True

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5
Q

What is reverse transcriptase?

A

RNA-dependent DNA polymerase

Found in the virions of retroviruses

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6
Q

Retroviruses of veterinary medicine were among the first retroviruses to be recognized. What are some important viruses and dates they were described?

A

Equine infectious anemia virus, bovine leukosis virus and jaagsiekte virus of sheep - 1800s

Retroviruses of chickens - 1908 in Denmark

Rous sarcoma virus (cattle, cats, primates and mice) - 1911

Since 1980 - we know that humans can get lymphomas, leukemia and AIDS

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7
Q

What are the two subfamilies of retroviridae?

A

Orthoretrovirinae

Spumaretrovirinae

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8
Q

What are the 6 genera of subfamily Orthoretrovirinae?

A 
Alpharetrovirus
Betaretrovirus
Gammaretrovirus
Deltaretrovirus
Epsilonretrovirus
Lentivirus
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9
Q

What is the only genus of subfamily Spumaretrovirinae?

A

Spumavirus

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10
Q

What are the characteristics of retroviruses?

A

Enveloped (lipid membrane bilayer) RNA viruses
Budding from the cell membrane
Surface is studded by envelope glycoproteins
Diploid genome with 2 copies of ss, + sense RNA
Integrate into the genome of the host by means of an enzyme called integrase

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11
Q

What shape are the virions of retroviruses?

A

Spherical

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12
Q

Retroviruses have a spherical layer of ______ beneath the envelope, an internal ______ protein which encloses the viral RNA = _______

A

Protein
Capsid
Nucleocapsid

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13
Q

What is inside of the retrovirus nucleocapsid?

A

Two ss viral RNA, reverse transcriptase, integrase and protease

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14
Q

Shape and position of the core were used to classify viruses into retroviral genera. What are the types of viruses and the locations of the core?

A

Type A - thick shell with a hollow electron-lucent center
Type B - round and eccentrically core
Type C - central, symmetrically placed core
Type D - distinct cylindrical core

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15
Q

T/f: Because virions are enveloped, they are easily inactivated by lipid solvents or detergents and by heating BUT are very resistant to UV or x-rays.

A

True

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16
Q

What is required for retrovirus replication?

A

RT

Each virion has at least 30 molecules of RT

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17
Q

Virions have at least 3-4 important genes. What are they?

A

Gag - encodes the virus core proteins (capsid, nucleocapsid, matrix)

Pol - encodes RT and integrase

Env - encodes virion envelope proteins, surface and transmembrane

Pro - encodes protease

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18
Q

Tell me about the characteristics of alpharetroviruses.

A

Simple retroviruses
Contains gag, pro, pol and env
Type C virion morphology
Represented by avian leukosis and sarcoma virus
Mostly endogenous and exogenous viruses of chickens

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19
Q

Exogenous retroviruses are those viruses transmitted how?

A

Horizontally and are rarely transmitted via in-utero or germline infection

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20
Q

Endogenous retroviruses are those viruses that…?

A

Included in the genome of most if not all animals.

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21
Q

What are the members of the alpharetrovirus genus?

A

Avian leukosis virus
Avian sarcoma virus
Avian myeloblastosis virus
Rous sarcoma virus

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22
Q

Tell me about Betaretroviruses

A

Mouse mammary tumor virus (MMTV)
Include gag, pro, pol and env
MMTV also has sag gene - encodes a superantigen
Contains both endogenous and exogenous retroviruses

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23
Q

Tell me about the gammaretroviruses

A 
Simple retroviruses
Type C morphology
Larges number of members 
Genome includes gag, pro, pol, and env
Contain both endogenous and exogenous retroviruses of mammals and reptiles
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24
Q

What are the 3 most important (for our class) of gammaretroviruses?

A

Feline leukemia virus
Feline sarcoma virus
Avian reticuloendotheliosis virus

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25
Tell me about deltaretroviruses
Complex with type C morphology Famous examples are: human T-lymphotropic virus (HTLV), bovine leukemia virus Genome contains gag, pro, pol, env and regulatory genes rex and tax Rex and Tax control synthesis and processing of viral RNA No known endogenous deltaretroviruses Exogenous are found only in a few mammals
26
Tell me about the epsilonretroviruses
Complex with type C morphology Prototype is the Walleye dermal sarcoma virus Contain gag, pro, pol and env; 3 additional genes termed ORF A, B, and C ORF A is a viral homologous of the host cyclin D and may regulate host cell cycle Only endogenous retroviruses found in fish and reptiles
27
Tell me about Lentiviruses
Complex with a cylindrical or conical shaped core MVPs: human immunodeficiency virus (HIV), caprine arthritis-encephalitis virus and meadi-visna virus Gag, pro, pol and env Slow viruses Accessory genes: vif, vpr, vpo, tat, rev, nef - control transcription, RNA processing, virion assembly, host gene expression Exogenous retroviruses are found in many mammals
28
Lentiviruses have nef genes that encode Nef proteins. What do the proteins do?
Is essential for replication in target hosts but not in cells culture in vitro. May down regulate expression of the CD4 molecule or alter the activation status of target cells
29
Lentiviruses also have a vif gene that encodes a protein Vif which does what?
Enhances replication in lymphocytes
30
Tell me about spumaviruses.
Complex viruses Exemplified by human foamy virus Virions are assembled in the cytoplasm and budded into endoplasmic reticulum (ER) and plasma membrane Gag, pro, pol and env, with accessory tas/bel-1 and bet Tas encodes a transcriptional activator Exogenous viruses in mammals
31
What are the steps in replication of retroviruses?
Receptor binding and membrane fusion -> internalization and uncoating -> Reverse transcription of the RNA genome to form linear dsDNA -> Nuclear entry of dsDNA -> integration of linear dsDNA into the host genome to form a provirus -> transcription of the provirus to form viral RNA -> splicing and nuclear export of RNA to the cytoplasm -> translation of the RNA to form precursor proteins -> assembly of virions and packaging of viral RNA genome -> budding and release of the virions -> proteolytic processing of the precursors and maturation of the virions
32
How do alpharetroviruses enter and initiate infection?
A membrane anchored glycoproteins with a sequence similar to ligand-binding repeat of the low-density lipoprotein receptor (LDLR)
33
How do Betaretroviruses enter the cell to initiate infection?
(MMTV) transferrin receptor tfr-1
34
How do Gammaretroviruses enter the cell and initiate infection?
Several receptors, mCat-1 for mouse viruses; GLVR1 for cat, dog and primate viruses; FeLIX and Pit for FeLV
35
How do Deltaviruses enter the cell and initiate infection?
Protein similar to AP-3 complex for BLV
36
How do Lentiviruses enter the cell and initiate infection?
CD4 on T helper cells, also expressed on macrophages and dendritic cells; CCR5 and CXCR4 expressed on lymphoid cells
37
What are the outcomes of retrovirus infection after penetration (sorry...) of virtual nucleic acids?
Virus induces transformation to malignancy Persistent infections -> chronic infection Latent infection Recurrence from latent infection -> viral multiplication and lytic infection -> release of virus by budding or lysis
38
Retroviruses that can lead to _____ transformation contain _____ ______
Acute; viral oncogenes
39
Retroviruses that cause _____ transformation do so by _____/mutation through random integration into the genome of the host
Chronic; insertion
40
Retroviruses acquire what during replication?
Cellular oncogenes
41
T/F: Viral oncogenes undergo mutations which usually removes the regulatory mechanisms
True
42
The retrovirus viral oncogenes may lead to transformation of the infected cells by acting how?
Growth factor Receptor Intracellular signal transducer Intranuclear transcription factor
43
Feline leukemia virus (FeLV) belongs to what genus affecting domestic cats worldwide?
Gammaretrovirus
44
There are three gammaretroviruses that felines can get, one exogenous and two endogenous, what are they?
Exogenous FeLV Endogenous feline leukemia virus (enFeLV) RD114
45
Does FeLV survive for long outside of the host?
No, they can be destroyed by disinfectants, soap, heating and drying making transmission via fomites unlikely
46
Which household is more likely to get FeLV: A. Lady with one cat, a boyfriend, a day job and a drinking problem OR B. Single lady with 7 cats eating in for the night drinking a glass of wine with all of her mittens watching RomComs on Hallmark?
B Because of the multiple number of cats, B has a 20% greater prevalence for FeLV where as A has a low prevalence around 1%
47
Who is the source of infection for FeLV and how is it transmitted?
The source is a cat infected with FeLV viremia. Shed from infected cat's saliva, nasal secretion, feces and milk. Transmitted mainly by mutual grooming but also bites. Risk factors for infection are young age, high population density and poor hygiene *Transmission from individual mammary gland is possible
48
What three outcomes are there to FeLV viremic infection in pregnant queens?
Embryonic death Stillbirth Viremic kittens
49
What age group of cats is more susceptible to FeLV?
Young kittens highly susceptible | Aged cats become somewhat resistant
50
What is the pathogenesis of FeLV?
Surface glycoproteins Infection through oral or pharyngeal associated tissue Spread through infected monocytes and lymphocytes Viremia develops with a few weeks Has tropism to lymphoid tissue Leads to immuno suppression Reduces the number of CD4+ T cells
51
What do we see with recurrent infections of FeLV?
Wasting syndrome and atrophy of the thymus Generally throw or no cellular immunity
52
FeLV viral protein p15e blocks T cell reactivity to what to IL?
IL-1 | IL-12
53
Our friend, the FeLV viral protein also blocks production of hematopoietic cells which leads to what?
Anemia
54
Immunosuppression from FeLV predisposed cats to other disease such as?
Infectious peritonitis Mycoplasmosis Toxoplasmosis Fungal infections
55
With FeLV, despite B cell infection, they still produce Ab which leads to?
deposition of Ab-Ag complexes -> gromerulonephritis
56
What are clinical signs of FeLV?
``` Immunosuppression Regenerative anemia Non-regenerative anemia Myelodestructin Myelosuppression Myeloproliferative disease Lymphoma Leukemia Other disease ```
57
How do we diagnose FeLV?
``` P27 ELISA Immunofluorenscence assay Virus isolation in culture Real-time PCR Reverse transcriptase PCR Serology - endogenous FeLV ```
58
How do we manage our FeLV?
FeLV-infected cats should be confined indoors to prevent spread to the whole neighborhood (cause clearly your cat is out mutual grooming the neighbor cat while the family is away). Minimize potential exposure to FeLV infected cats to other infectious agents
59
To vaccinate or not to vaccinate for FeLV,that is the question.
No FeLV vaccine provides complete (100% efficacy) protection and none prevents infection
60
What is Feline immunodeficiency virus (FIV)?
``` A lentivirus (slow virus) Disease called Feline immunodeficiency Approximately 2.5% of cats in US have FIV ```
61
What is the pathogenesis of FIV?
Replicates in lymphocytes, mostly CD4+ T cells, B cells and macrophages -> binds to CD134 and CD184 on activated CD4+ -> infection of CD4+ cells leads reduction of this cell type -> reduction of IL-2 production -> lymphopenia -> FIV activates CD4+/CD25+ Treg - depends immunosuppression -> increases IL-10 production - immunosuppression
62
When was FIV first discovered?
UC Davis in 1986 by Janet Yamamoto and Niels Pederson
63
What is the signalment of FIV?
Infects domestic cats Wild cats: snow leopards, lions, tigers, jaguars, Florida panthers, bobcats
64
How is FIV transmitted?
Primary modes are deep bite wounds and scratches Sexual contact is NOT a major means of spreading FIV Occasionally mother to kitten but FIV transmission in utero is rare
65
What are the clinical signs of of FIV?
``` Persistent fever Loss of appetite and lethargy Gingivitis, stomatitis, chronic or recurrent skin, urinary bladder and upper respiratory tract infections Slow weight loss and severe wasting Cancer and blood disease Abortions ```
66
What are the diagnostic tests for FIV?
ELISA - antigens and anti-FIV antibodies Immunoblotting PCR
67
What is the recommended treatment for FIV?
NONE to eliminate virus | Treated symptomatically - nutritional support, fluid therapy, dental care
68
How do we prevent FIV?
Isolated affected cats Keep unaffected cats away from feral cats Vaccine for FIV is currently available Spaying and neutering outdoor cats can limit exposure by decreasing aggressive behaviors
69
Tell about vaccines for FIV. Do they exist? Do they provide full protection? What do you need to know for future testing?
Yes, they are available. Do not provide full protection FIV antibody positive
70
What genus does Equine infectious anemia virus belong to? What disease does it cause?
Lentivirus Causes Swamp Fever - peracute (rare) or acute/chronic disease Inapparent - asymptomatic carriers
71
How is Swamp fever transmitted?
Blood (instruments/insects) | Virus in all secretions - venereal, in utero, milk, colostrum
72
When swamp fever is transmitted by insects, there are two possible scenarios, what are they?
If the fly feeding is uninterrupted the virus is inactivated before next blood meal and there is no transmission If the feeding by the fly is interrupted, it will try to feed on another horse, the virus can be transmitted then
73
What is the pathogenesis of chronic equine infectious anemia virus?
Initially infects monocytes but cannot replicate in them. Monocytes enter the tissues and become macrophages where the virus can replicate -> spreads to lymphocytes Antibodies mediate phagocytosis and complement mediated lysis and RBCs Leads to anemia and thrombocytopenia
74
What are the two clinical signs that happen with secondary infection of thrombocytopenia with equine infectious anemia?
Petechial hemorrhage | Edema
75
What are the clinical signs of equine infectious anemia virus?
``` Anemia Lethargy Weight loss Fever Enlarged spleen Swollen belly and legs (edema) Depression Decreased athletic performance Death (in acute cases) ```
76
What are the diagnostic tests for Equine infectious anemia virus?
Agar gel immunodiffusion (AGID or Coggin's test) ELISA kit (replaced AGID) Immuno-blot Complement ELISA (cELISA)
77
What are the animal movement restrictions?
Horses imported to USA and Canada may require a negative test certificate.

RUSVM Virology (10 decks)

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