Finals: Retroviridae Flashcards
How did retrovirus get it’s name?
Have important enzymes they encode for reverse transcriptase
Retroviruses infect ___ and ___
Animals and humans
Wow, tell me more….
Retroviruses can be the causative agents for what?
Cancer
Immunosuppression
Immunodeficiency diseases
T/F: retroviruses may exist as stable components in the host genome
True
What is reverse transcriptase?
RNA-dependent DNA polymerase
Found in the virions of retroviruses
Retroviruses of veterinary medicine were among the first retroviruses to be recognized. What are some important viruses and dates they were described?
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
What are the two subfamilies of retroviridae?
Orthoretrovirinae
Spumaretrovirinae
What are the 6 genera of subfamily Orthoretrovirinae?
Alpharetrovirus Betaretrovirus Gammaretrovirus Deltaretrovirus Epsilonretrovirus Lentivirus
What is the only genus of subfamily Spumaretrovirinae?
Spumavirus
What are the characteristics of retroviruses?
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
What shape are the virions of retroviruses?
Spherical
Retroviruses have a spherical layer of ______ beneath the envelope, an internal ______ protein which encloses the viral RNA = _______
Protein
Capsid
Nucleocapsid
What is inside of the retrovirus nucleocapsid?
Two ss viral RNA, reverse transcriptase, integrase and protease
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?
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
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.
True
What is required for retrovirus replication?
RT
Each virion has at least 30 molecules of RT
Virions have at least 3-4 important genes. What are they?
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
Tell me about the characteristics of alpharetroviruses.
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
Exogenous retroviruses are those viruses transmitted how?
Horizontally and are rarely transmitted via in-utero or germline infection
Endogenous retroviruses are those viruses that…?
Included in the genome of most if not all animals.
What are the members of the alpharetrovirus genus?
Avian leukosis virus
Avian sarcoma virus
Avian myeloblastosis virus
Rous sarcoma virus
Tell me about Betaretroviruses
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
Tell me about the gammaretroviruses
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
What are the 3 most important (for our class) of gammaretroviruses?
Feline leukemia virus
Feline sarcoma virus
Avian reticuloendotheliosis virus
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
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
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
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
Lentiviruses also have a vif gene that encodes a protein Vif which does what?
Enhances replication in lymphocytes
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
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
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)
How do Betaretroviruses enter the cell to initiate infection?
(MMTV) transferrin receptor tfr-1
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
How do Deltaviruses enter the cell and initiate infection?
Protein similar to AP-3 complex for BLV
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
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
Retroviruses that can lead to _____ transformation contain _____ ______
Acute; viral oncogenes
Retroviruses that cause _____ transformation do so by _____/mutation through random integration into the genome of the host
Chronic; insertion
Retroviruses acquire what during replication?
Cellular oncogenes
T/F: Viral oncogenes undergo mutations which usually removes the regulatory mechanisms
True
The retrovirus viral oncogenes may lead to transformation of the infected cells by acting how?
Growth factor
Receptor
Intracellular signal transducer
Intranuclear transcription factor
Feline leukemia virus (FeLV) belongs to what genus affecting domestic cats worldwide?
Gammaretrovirus
There are three gammaretroviruses that felines can get, one exogenous and two endogenous, what are they?
Exogenous FeLV
Endogenous feline leukemia virus (enFeLV)
RD114
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
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%
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
What three outcomes are there to FeLV viremic infection in pregnant queens?
Embryonic death
Stillbirth
Viremic kittens
What age group of cats is more susceptible to FeLV?
Young kittens highly susceptible
Aged cats become somewhat resistant
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
What do we see with recurrent infections of FeLV?
Wasting syndrome and atrophy of the thymus
Generally throw or no cellular immunity
FeLV viral protein p15e blocks T cell reactivity to what to IL?
IL-1
IL-12
Our friend, the FeLV viral protein also blocks production of hematopoietic cells which leads to what?
Anemia
Immunosuppression from FeLV predisposed cats to other disease such as?
Infectious peritonitis
Mycoplasmosis
Toxoplasmosis
Fungal infections
With FeLV, despite B cell infection, they still produce Ab which leads to?
deposition of Ab-Ag complexes -> gromerulonephritis
What are clinical signs of FeLV?
Immunosuppression Regenerative anemia Non-regenerative anemia Myelodestructin Myelosuppression Myeloproliferative disease Lymphoma Leukemia Other disease
How do we diagnose FeLV?
P27 ELISA Immunofluorenscence assay Virus isolation in culture Real-time PCR Reverse transcriptase PCR Serology - endogenous FeLV
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
To vaccinate or not to vaccinate for FeLV,that is the question.
No FeLV vaccine provides complete (100% efficacy) protection and none prevents infection
What is Feline immunodeficiency virus (FIV)?
A lentivirus (slow virus) Disease called Feline immunodeficiency Approximately 2.5% of cats in US have FIV
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
When was FIV first discovered?
UC Davis in 1986 by Janet Yamamoto and Niels Pederson
What is the signalment of FIV?
Infects domestic cats
Wild cats: snow leopards, lions, tigers, jaguars, Florida panthers, bobcats
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
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
What are the diagnostic tests for FIV?
ELISA - antigens and anti-FIV antibodies
Immunoblotting
PCR
What is the recommended treatment for FIV?
NONE to eliminate virus
Treated symptomatically - nutritional support, fluid therapy, dental care
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
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
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
How is Swamp fever transmitted?
Blood (instruments/insects)
Virus in all secretions - venereal, in utero, milk, colostrum
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
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
What are the two clinical signs that happen with secondary infection of thrombocytopenia with equine infectious anemia?
Petechial hemorrhage
Edema
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)
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)
What are the animal movement restrictions?
Horses imported to USA and Canada may require a negative test certificate.
