Flashcards in Final Exam - Retroviridae Deck (72):
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.
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.
Morphology - Type A virus
Form extracellular structures with a characteristically thick shell with a hollow electron lucent ceter
Morphology - Type B virus
Show a round but eccentrically positioned inner core
Morphology - Type C virus
Assemble at plasma membrane and contain a central symmetrically placed spherical inner core
Morphology - Type D virus
Assemble in the cytoplasm via an A type intermediate and budding, show a distinct cylindrical core
Virion properties - gag
gag gene encodes the virus core proteins. Capsid, nucleocapsid, matrix
Virion properties - pol
pol gene encodes: reverse transcriptase and integrase
Virion properties - env
env gene encodes: viral envelop proteins, surface, and transmembrane
Virion properties - pro
gene encodes the protease
Simple retroviruses. Represented by avian leukosis and sarcoma virus (ALSV). Contains gag, pro, pol and env. Mostly endogenous and exogenous viruses of chickens.
Those viruses transmitted horizontally and are rarely transmitted via in-utero or germline infection.
(retroviral elements) are those viruses included in the genome of most if not all animals.
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.
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.
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.
Rex and Tax Genes
Expressed from an alternatively spliced mRNS. Control synthesis and processing of viral RNA.
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.
Is a viral homologue of the host cyclin D and may regulate host cell cycle
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.
vif, vpr, vpo, tat, rev, and nef. Control transcription, RNA processing, virion assembly, host genes expression.
in lentiviruses, it encodes a transactivator that enhances the efficiency of cellular RNA polymerase
in lentiviruses, encodes a protein that facilitates transport of non-spliced viral RNA from the nucleus to the cytoplasm.
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.
encodes a protein vif which enhances replication in lymphocytes
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
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.
Alpharetroviruses Receptor Binding
A membrane anchored glycoprotein with a sequence similar to ligand binding repeat of the low density lipoprotein receptor (LDLR)
Betaretroviruses Receptor Binding
MMTV transferring receptor tfr-1
Gammaretroviruses Receptor Binding
Several receptors, mCat-1 for mouse viruses; GLVR1 for cat, dog, and primate viruses; FeLIX and Pit for FeLV
Deltaretroviruses Receptor Binding
A protein similar to AP-3 complex for BLV
Lentiviruses Receptor Binding
CD4 on T helper cells, also expressed on macrophages and dendritic cells; CCR5 and CXCR4 expressed on lymphoid cells
Contain viral oncogenes (v-onc)
They do so by insertion/mutation through random integration into the genome of the host
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.
Feline Leukemia Virus (FeLV)
Is a gammaretrovirus affecting domestic cats. Contain 3 genes: env, pol and gag.
Two forms of Endogenous Gammaretroviruses
1. Endogenous Feline Leukemia Virus (enFeLV)
2. RD114 Virus
Subtype A FeLV
Ubiquitous and involved in every infection
Subtype B FeLV
Originates from recombination of FeLV A with enFeLV
Subtype C FeLV
Result of mutations in the env gene of FeLV
Subtype T FeLV
Has a tropism for T lymphocytes
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.
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.
FeLV Clinical signs
Immunosuppression. Regenerative anemia. Non-regenerative anemia, myelodestruction, myelosuppression and myeloproliferative. Lymphoma and leukemia.
p27 ELISA. Immunofluorescence assay (IFA). Virus isolation in cell culture. Real-time PCR. Reverse transcriptase PCR. Serology.
No FeLV vaccine provides complete (100% efficacy) protection and none prevents infection.
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.
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
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.
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.
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.
FIV - Diagnostic Tests
ELISA to detect antigens and antibodies (does not work well with very early infection. Immunoblotting, PCR.
FIV - Treatment
No treatment to eliminate the virus. Most are dental care.
FIV - Prevention
Spaying and neutering outdoor cats can limit exposure by decreasing aggressive behaviors.
FIV - Vaccination
FIV Vaccine is available. Does not provide full protection. FIV antibody positive result for cats that are vaccinated.
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)
Avian Retrovirus - Endogenous
Occur in the genome of chickens as provirus
Avian Retrovirus - Exogenous Replication Competent
Usually not pathogenic, but may cause disease in a small percentage of chicken poulation
Avian Retrovirus - Exogenous replication defective
May acquire v-onc and induce malignant tumors rapidly
Avian Retrovirus - An exception
Rous sarcoma virus has full viral genes plus a v-onc and may rapidly induce oncogenesis
Avian Retrovirus - Oncogenic Viruses
Are transmitted horizontally or vertically through infectious virus or provirus integrated into host germ cells DNA
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.
Thick leg syndrome. Caused my replication defective avian retrovirus. May have secondary anemia and lymphoid leukosis.
Example of cellular transformation of oncogenic viruses. Presence of erythroblasts in blood. The targets are progenitor erythroblasts.
Equine Infectious Anemia Virus (Swamp Fever)
A lentivirus. Peracute (rare) or acute/chronic disease. Inapparent - asymptomatic carriers
Equine Infectious Anemia Virus (Swamp Fever) - Transmission
Blood (instruments or insect bites). Secretions (venereal, utero, milk/colostrum)
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.
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
Equine Infectious Anemia Virus (Swamp Fever) - Clinical signs
Anemia, fever, swollen belly and legs (edema), decrease athletic performance.
Equine Infectious Anemia Virus (Swamp Fever) - Diagnostic Tests
AGID or Coggin's Test. ELISA kit (replaced AGID).