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Flashcards in Final Exam - Retroviridae Deck (72):
1

Retroviridae

Causative agents of some types of cancer, immunosuppression or immunodeficiency disease. May exists as stable components in the host gene. Retro = reverse/backward. Uses the RNA genome to produce DNA intermediates by means of RNA dependent DNA polymerase.

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Retroviridae Implication

They integrate into the genome of the host by means of an enzyme called integrase. They may alter or acquire host genome sequences, may activate or inactivate particular host genes located near the integration site.

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Morphology - Type A virus

Form extracellular structures with a characteristically thick shell with a hollow electron lucent ceter

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Morphology - Type B virus

Show a round but eccentrically positioned inner core

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Morphology - Type C virus

Assemble at plasma membrane and contain a central symmetrically placed spherical inner core

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Morphology - Type D virus

Assemble in the cytoplasm via an A type intermediate and budding, show a distinct cylindrical core

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Virion properties - gag

gag gene encodes the virus core proteins. Capsid, nucleocapsid, matrix

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Virion properties - pol

pol gene encodes: reverse transcriptase and integrase

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Virion properties - env

env gene encodes: viral envelop proteins, surface, and transmembrane

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Virion properties - pro

gene encodes the protease

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Alpharetroviruses Characteristics

Simple retroviruses. Represented by avian leukosis and sarcoma virus (ALSV). Contains gag, pro, pol and env. Mostly endogenous and exogenous viruses of chickens.

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Exogenous retroviruses

Those viruses transmitted horizontally and are rarely transmitted via in-utero or germline infection.

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Endogenous retroviruses

(retroviral elements) are those viruses included in the genome of most if not all animals.

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Betaretroviruses

Simple retroviruses. Have type B morphology with round eccentric core or type D with cylindrical core. The genomes contain gag, pro, pol, and env genes. Mouse Mammaroy Tumor Virus (MMTV) has a sag gene that encodes superantigen.

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Gammaretroviruses

Simple retroviruses with a C type morphology. Has the largest number of members e.g., murine leukemia virus, feline leukemia virus. Genome contains gag, pro, pol, and env. Contain both endogenous and exogenous retroviruses of mammals and reptiles.

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Deltaretroviruses

Complex retroviruses with a C-type morphology. Human T-lymphotrophic virus (HTLV), bovine leukemia virus. Genome contains gag, pro, pol, env, and regulatory genes, rex and tax. No known endogenous deltaretroviruses. Exogenous retroviruses are found in a few mammals.

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Rex and Tax Genes

Expressed from an alternatively spliced mRNS. Control synthesis and processing of viral RNA.

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Epsilonretroviruses

Complex retroviruses with a type C morphology. Walleye dermal sarcoma virus. Contain gag, pro, pol, and env. Also genes ORF A, B, C. Only endogenous retroviruses are found in fish and reptiles.

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ORFa

Is a viral homologue of the host cyclin D and may regulate host cell cycle

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Lentiviruses

Complex viruses with a cylindrical or conical shaped core. Human immunodeficiency virus (HIV) and caprine arthritis-encephalitis virus and visna virus. Contains gag, pro, pol, env. ALso contains accessory genes. Exogenous retroviruses are found in many mammals.

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Accessory genes

vif, vpr, vpo, tat, rev, and nef. Control transcription, RNA processing, virion assembly, host genes expression.

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tat gene

in lentiviruses, it encodes a transactivator that enhances the efficiency of cellular RNA polymerase

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rev gene

in lentiviruses, encodes a protein that facilitates transport of non-spliced viral RNA from the nucleus to the cytoplasm.

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nef gene

in lentiviruses, encodes Nef protein that: is essential for replication in target hosts but no in cell culture in vitro. May down regulate expression of the CD4 molecule or alter the activation status of target cells.

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vif gene

encodes a protein vif which enhances replication in lymphocytes

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Spumaviruses

Complex viruses with a unique virion morphology containing spikes on the surface. Human foamy virus. Contains gag, pro, pol, env. Accessory genes (tas/bel-1, and bet). Exogenous viruses

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tas gene

Transcriptional activator

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Retrovirus Receptor Binding

To enter a cell and initiate infection, retroviruses require interaction between a cell surface molecule (receptor) and the envelope proteins on the virion surface.

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Alpharetroviruses Receptor Binding

A membrane anchored glycoprotein with a sequence similar to ligand binding repeat of the low density lipoprotein receptor (LDLR)

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Betaretroviruses Receptor Binding

MMTV transferring receptor tfr-1

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Gammaretroviruses Receptor Binding

Several receptors, mCat-1 for mouse viruses; GLVR1 for cat, dog, and primate viruses; FeLIX and Pit for FeLV

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Deltaretroviruses Receptor Binding

A protein similar to AP-3 complex for BLV

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Lentiviruses Receptor Binding

CD4 on T helper cells, also expressed on macrophages and dendritic cells; CCR5 and CXCR4 expressed on lymphoid cells

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Acute Transformation

Contain viral oncogenes (v-onc)

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Chronic Transformation

They do so by insertion/mutation through random integration into the genome of the host

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Oncogenesis

Cellular oncogenes are required for normal cell growth and differentiation. Cellular oncogenes (c-onc) during replication. These acquired c-onc become viral oncogenes (v-onc). Viral oncogenes undergo mutations which usually removes the regulatory mechanisms. Act as growth factors, receptors, intracellular signal transducers or intranuclear transcription factors.

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Feline Leukemia Virus (FeLV)

Is a gammaretrovirus affecting domestic cats. Contain 3 genes: env, pol and gag.

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Two forms of Endogenous Gammaretroviruses

1. Endogenous Feline Leukemia Virus (enFeLV)
2. RD114 Virus

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Subtype A FeLV

Ubiquitous and involved in every infection

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Subtype B FeLV

Originates from recombination of FeLV A with enFeLV

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Subtype C FeLV

Result of mutations in the env gene of FeLV

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Subtype T FeLV

Has a tropism for T lymphocytes

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FeLV Transmission

Virus is shed from saliva, nasal secretions, feces, and milk. Mutual grooming and through bites. Cats with FeLV viremia act as a source of infection.

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FeLV Pathogenesis

The SU protein (surface glycoprotien) is the main determinant of pathogenecity. Infection ensures through oral or pharyngeal associated tissue. Virus spread to peripheral tissues through infected monocytes and lymphocytes. Viremia develops within a few weeks of infection. FeLV has tropism to lymphoid tissue. Leads to immunosuppression and reduced the number of CD4+ T cells.

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FeLV Clinical signs

Immunosuppression. Regenerative anemia. Non-regenerative anemia, myelodestruction, myelosuppression and myeloproliferative. Lymphoma and leukemia.

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FeLV Diagnostics

p27 ELISA. Immunofluorescence assay (IFA). Virus isolation in cell culture. Real-time PCR. Reverse transcriptase PCR. Serology.

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FeLV Vaccination

No FeLV vaccine provides complete (100% efficacy) protection and none prevents infection.

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Feline Immunodeficiency Virus (FIV)

A lentivirus ("slow virus") has a long incubation period. It attacks the immune system and so weakens the immune response to infections and cancers.

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FIV Pathogenesis

Replicates in lymphocytes, mostly CD4+ T cells, B cells and macrophages. CD134 and CD184 (CXCR4) on aactivated CD4+ cells. FIV activates CD4+/CD25+ Treg - deepens immunosuppression

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FIV Signalment

Vulnerable at any age. Outdoor free-roaming felines are at greater risk. More predominant in free-roaming aggressive male cats. Infects domestic cats and wild felines.

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FIV Transmission

Deep bite wounds and scratches. Sexual contact is NOT a major means of spreading FIV. Occasionally transmitted from infected mother cat to kittens. Transmission in utero or in milk is very rare.

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FIV Clinical signs

Persistent fever. Loss of appetite and lethargy. Gingivitis and stomatitis and chronic or recurrent skin, urinary bladder and upper respiratory tract infection. Slow but progressive weight loss and severe wasting. Cancer and blood diseases. Abortions.

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FIV - Diagnostic Tests

ELISA to detect antigens and antibodies (does not work well with very early infection. Immunoblotting, PCR.

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FIV - Treatment

No treatment to eliminate the virus. Most are dental care.

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FIV - Prevention

Spaying and neutering outdoor cats can limit exposure by decreasing aggressive behaviors.

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FIV - Vaccination

FIV Vaccine is available. Does not provide full protection. FIV antibody positive result for cats that are vaccinated.

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Avian Leukosis and Sarcoma Viruses

Retroviruses that infect chickens belong to two groups.

1. Alpharetroviruses (avial leukosis, myeloblastosis and sarcoma virus)
2. Gamma retroviruses (reticuloendotheliosis virus)

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Avian Retrovirus - Endogenous

Occur in the genome of chickens as provirus

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Avian Retrovirus - Exogenous Replication Competent

Usually not pathogenic, but may cause disease in a small percentage of chicken poulation

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Avian Retrovirus - Exogenous replication defective

May acquire v-onc and induce malignant tumors rapidly

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Avian Retrovirus - An exception

Rous sarcoma virus has full viral genes plus a v-onc and may rapidly induce oncogenesis

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Avian Retrovirus - Oncogenic Viruses

Are transmitted horizontally or vertically through infectious virus or provirus integrated into host germ cells DNA

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Lymphoid Leukosis

Disease caused by avian retroviruses. No specific clinical signs. Tumors may develop. Nodular lesions in bursa fabricius. Large amounts of IgM but no class switch.

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Osteopetrosis

Thick leg syndrome. Caused my replication defective avian retrovirus. May have secondary anemia and lymphoid leukosis.

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Erythroblastosis

Example of cellular transformation of oncogenic viruses. Presence of erythroblasts in blood. The targets are progenitor erythroblasts.

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Equine Infectious Anemia Virus (Swamp Fever)

A lentivirus. Peracute (rare) or acute/chronic disease. Inapparent - asymptomatic carriers

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Equine Infectious Anemia Virus (Swamp Fever) - Transmission

Blood (instruments or insect bites). Secretions (venereal, utero, milk/colostrum)

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Equine Infectious Anemia Virus (Swamp Fever) - Transmission of virus by insects

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.

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Equine Infectious Anemia Virus (Swamp Fever) - Pathogenesis (Chronic Infection)

Initially infects monocytes but cannot replicate in them. Monocytes enter the tissue and become macrophages and virus replication begins. Virus spreads to lymphocytes. Ab mediate phagocytosis and complement mediated lysis of RBC. Leads to anemia and thormbocytopenia

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Equine Infectious Anemia Virus (Swamp Fever) - Clinical signs

Anemia, fever, swollen belly and legs (edema), decrease athletic performance.

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Equine Infectious Anemia Virus (Swamp Fever) - Diagnostic Tests

AGID or Coggin's Test. ELISA kit (replaced AGID).

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False reactions on Coggin's Test

False positive - foal with passive Ab

False negative - recently infected horse