Medical Virology PATB 4710
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Date Created: 10/27/15
Feline Leukemia Virus Feline leukemia virus FeLV is a veterinary important disease It is highly contagious anal causes immunosuppression in cats Written by Casey Maunder Chiwah Lam Jaquenette McNeil and Kali Maris Medical Virology Fall Semester 2006 University of Wyoming Contents links on homepage gt Introduction gt Epidemiology amp Etiology gt TransmissionExposure gt Pathogenesis gt Structural Characteristics gt Transmission gt Epidemiology and Exposure gt Clinical Signs amp Symptoms gt Diagnosis gt Treatment gt PreventionControl gt Vaccine gt Prognosis gt Geographical Distribution amp Statistics gt Molecular Biology of the Virus gt Test Procedures gt Case Studies gt References and links Introduction Every year 1000s of domestic cats amp kittens are euthanized based upon positive FeLV testing This is devastating to pet owners and although not 100 preventable infection rate can be reduced to less than 2 through conscientious vaccination regime and simple preventive measures Epidemiology amp Etiology Feline leukemia virus belongs to the Retroviridae family genus Gammaretrovirus This virus exists in four sub types A B C and T FeLViA is the most common of the three and is found in all infected animals FeLVA is considered the least pathogenic although cats infected with FeLVA are at great risk of developing severe immunosuppressive disease FeLVA recombination in vivo produces the other subtypes thereby making sub type A the only transmissible form Viral recombination leading to co infection of A with any one of the other three can lead to a higher incidence of tumors or anemia associated with erythroid hypoplasia Types of FeLV The virus is broken into three groups based upon their occurrence and the effects they have on the host Infected hosts can have one two or all types of virus GrouB Occurrence Effects FeLVA occurs in all FeLV infected cats causes severe immunosuppression FeLVB occurs in 50 of FeLV infected cats causes more tumors FeLVC occurs in 1 of FeLV infected cats causes severe anemia FeLVT new emerging subtype causes immunodeficiencyinducing cytopathic effects The Merck Veterinary Manual 2006 Transrn nEgnmr Fellne leukemla vlrus ls a naturally oeeurnng vlrus andlts lncldence ls a ddrect conelatlon to populahon denslty Infectlon rates are hlghestln Bananas rnulhple cat households and cats that are free roarnrng whether feral or allowed outslde aeeess by owners Perslstendy lnfected healthy cats are the major reservolr ofFeLV Carners excrete large quanmles of vlrus m sallva There are up to 10 lnfeeuous FeLV parheles excreted per mllllllter of salwa Keller et al 2005 muml r mm lluer boxes sneezrng bmng and bloodtransfuslons klttens fraglle nature ofthls enveloped vlrus Pathngenesls FeLVA ls foundln all FeLV mfected cats and eauses severe lrnrnunosupresslon FeLVD FeLV 2005 FeLV related disorders include immunosuppression leukemia immunemediated diseases reproductive problems and enteritis FeLV related immunosuppression causes increased susceptibility to bacterial fungal protozoal and other viral infections Lymphoid or myeloid leukemia develops in a thde of FeLV persistent infections and the virus is thought to also promote lymphoma in infected cats Leukemia in cats is strongly associated With FeLV infection that causes neoplasia in neutrophils basophjls eosinophils monocytes lymphocytes megakaryoctes and erythrocytes Immunemediated diseases include systemic vasculitis glomerulonephritis and polyarthritis Reproductive problems are common in FeLV infected cats over half of the infertile queens and queens that abort are FeLV positives Enteritis caused by FeLV manifests With clinical signs such as anorexia depression vomiting and diarrhea Merck 2006 wwwvetugaeduVPPclerkiyerindexhtm Neonatal deaths associated with feline leukemia virus infection image courtesy of Noah39s Arkive the University of Georgia There are six stages of feline leukemia infections Stage 1 The virus enters the cat through the pharynx infecting the local epithelial cells lymphocytes and macrophages The infected White blood cells disseminate to lymph nodes and begin to replicate Stage 2 Primary or transient viremia a brief presence of the virus in the blood stream and dissemination of the virus to lymphoid system Stage 3 The lymphoid system is infected and the virus further disseminates throughout the body Necropsy ofFeLV infected cat showing acutehanorrhages m colon sa osal surface andregional lymph nodes Cornell 2006 1 Stage 4 The hemolymphatic system and intestinal tissues are infected Unless the cat s immune system ghts off the virus the disease continues to develop into stage 5 Stage 5 Secondary or persistent viremia is established The bone marrow becomes infected and releases infected neutrophils and platelets into the blood Stage 6 The cat body is overwhelmed by the infection and the virus starts to appear in mucosal and glandular epithelial cells Paustian 1999 About 40 of the FeLV infected cats develop immunity and eliminate the virus with 16 of these successful viral eliminations due to minimal exposure to the virus The other 24 confers resistance to the disease at stage 4 which occurs around 1618 weeks after the infection began About 20 of the cats enter a latent stage in where reactivation of the disease occurs when the cat becomes stressed About 510 of the cats enter a sequestered stage in which viremia is limited intermittent or even absent The remaining 30 of cats go through the disease from stage one to six resulting in death due to any of the feline leukemia associated diseases Iyer 2005 Cats diagnosed with FeLV persistent infection may die in months or stay asymptomatic for up to 4 years FeLV cats that develop immunity to the virus may shed infectious FeLV during the transient viremia lasting from one to two days and for as long as eight weeks FeLV cats with persistent viremia shed virus for the rest of their lives and serve as a source of infection to susceptible cats Paustian 1999 FeLV hlndllmb paralysls and anlsocona unequal slze othe puplls Moreover eats wth FeLV are suseeptrble to other dlseases especlally HA Fellne Infectlous Anemla or Hemobartohellosrs www1h ahcnmfalinvfelvhtrnl A svmptoms ofFeLV meluole fever persrsteht eough labored breathlng vomruhg decreased vverght loss of appeme mouth sores and frequent lnfecnons Besldes these symptoms more severe slgns othls vlral lnfectlon may emst sueh as tumors anemla ehtehus wth assoerateol bloody dlanhea smolreproolueuve problems Cats presenting with the abovedescribed symptoms should be tested for feline leukemia in clinic using the ELISA snap test The ELISA is a soluteantigen test that detects free antigen in uid and is most reliable when serum or plasma is tested The following are the steps to run an ELISA snap test from WWWlbahc0mfeinefelvhtml Specialized equipment and training is needed to accurately run the ELISA test The bottle with the dark blue top is the reagent used to start the chemical reaction needed to read the test A few drops ofblood are all that is needed The test kit the blood will be placed into is called a Snap test because the right hand side of it is snapped down to complete the test After being placed in the reagent solution the blood is transferred to the diagnostic test kit well The blood immediately starts owing towards the white circle in the center of the test kit It takes 3060 seconds to reach the white circle When the blood ow reaches the center crrcle the kn rs actwated by pushnlg down on the elevated area on the ght srde ofthe test kn A ex a few seconds the blood starts owmg back to the le The blood eventually ows all the way back to Its starting point A ex 10 nnnutes a blue dot appears srgnrfyrng that thrs cat 5 negatrye for both FeLv and FIV The three drfferent type ofposlbve results that are possrble FeLv Posrtrve FELV and FIV FIV Posrtrve Posxbve There 5 an addmonal test for the FeLv called the IFA Imrnuno uorescent Anubody test that checks for evxdence of the wrus m whrte blood cells Th test 5 used to con ml a poslbve ELISA test and n 5 mdlcauve ofa persrstent rnfectron It rs not used as an unhal blood slream TheIFA tests for the presence ofFeLV structural antlgens eg p27 or oLher lnfected In cllnlcal pmctlce penpheralblood smears are usually used fortheIFA LesL but cytologlcal preparauorrs ofbone marrow can alsobe used PC shown hae fw i r i 2 39quot quot r a a con rmed by IFA lrnmuno uourescmt assay or PCR amplrfreauon Cats erh negauye results and ymplomaue should also have IFA or PCR lesls performed Tests perfurmed in Lhe WSV39L The V l leukemla yrrus FeLV antlgen and fellne lmmunodeflclency yrrus HV Daemon ofFeLV lndlcates that a cathas been arposedlo HV Treatment There is currently no cure for feline leukemia However it is possible for cats to develop antibodies against the virus and ght it off on their own There are some treatment options for the disease mostly aimed at ghting other infections that can occur in the immunosuppressedinfected cat These treatments are not to cure the disease but to make the cat s quality of life better by treating other diseases caused by the viral infection Antibiotics can be used to fight off bacterial infections and cortisone has been used somewhat successfully to reduce tumors in infected cats Additionally medications can be administered that help to increase immune function including immunoregulin and interferon Since infected cats often have no appetite they do not receive the necessary nutrients they need aiding to a weakened immune system Vitamin supplements can be given orally to help the cat replenish its exhausted nutrients Feline leukemia causes pain and suffering to the host s owner so because of this many individuals choose to euthanize their cat All regular vaccinations should be continued with killed virus except in the case of the FeLV vaccine Secondary infections must be addressed due to the limited immune response of the animal Antibiotics steroids vitamins RBC enhancers and immune stimulants are recommended Drugs that used in human medicine have had some success in treating cats and in some cases a 50 mortality rate was reduced by about 20 These drugs include AZT and Interferon Omega PreventionControl Prevention of FeLV is simple limit exposure keep the cat inside and follow the vaccination protocol of a veterinarian All new cats brought into the household should be tested for feline leukemia and for those allowed indooroutdoor access the vaccine becomes necessary In addition the virus can be transmitted by fomites Infected cats need to be isolated and removed from the home Contaminated food water dishing bedding and litter ll boxes should be cleaned or discarded The ef ciency of the FeLV vaccine is approximately 80 Vaccine There are several killed virus vaccines for feline leukemia virus that is very effective and should be given to all cats and kittens that are not already infected especially if the cat is going to be around other cats It can be given to kittens when they are 9 weeks old with a booster given 24 weeks later and followed by a yearly booster lime Leukemia Vaccine r s F 71a 9 Any names Vaccine Antigen Any Leukamla Virus Antigen WWWlbahcomfelinefelvhtml Vaccines containing leukemia virus antigen other antigens should be administered in the left rear region LR according to manufacturer39s recommendations FeLV 2 doses 1 year later Follow testing recommendations as published in the AAFPAFM killed 34 Wks then annually Recommendation for Feline Retrovirus Testing Recommended for a art use in cats with high risk of exposure 1st dose gt 8 Wks 2nd dose gt12 Wks Prognosis There is no speci c treatment for feline leukemia and no known cure Cats with cancer associated with FeLV have an average survival time of six months Geographical Distribution amp Statistics Noted for its attack on felids FeLV is one of the most devastating feline diseases worldwide However the frequency of infection varies greatly depending on the cat s age health environment and lifestyle Cornell 2006 Furthermore cats that are young or old ill and live outside have a 13 higher chance of becoming infected Only about 3 of American cats contract this disease Harms 2006 Males are ll 2 times more likely to be infected than females Nash 1997 Cats that have severe bacterial infections and cats with toxoplasmosis will have a 50 and 75 chance of also having FeLV infections Animal Health Channel 2006 Though these numbers are relatively high the largest infectious rates are in catteries and multicat homes All and all this disease is very serious and it is estimated that less than 20 of infected cats will survive more than three years after being infected Saidla et al 2006 Molecular Biology of the Virus from Principles of Virology Flint 2000 Retrovirus life cycle Attachment uncoding replication and release of FeLV virion Structural Characteristics Feline leukemia virus is a member of the family Retroviridae and has a single stranded RNA ssRNA nucleic acid There is considerable diversity between various types of retrovirus the following is a generalized description of the particle There is a universal nomenclature for retrovirus proteins Table l The eight proteins above are necessary for replication The SU glycoprotein is responsible for receptor binding the TM glycoprotein holds the SU glycoprotein to the envelope and is responsible for membrane fusion The MA protein is located inside the membrane and has an amorphous shape and the CA protein is also inside the membrane and is icosahedral Feline leukemia virus is a tumorcausing virus Cornell University 2006 This virus has Transmembrane Glycoprotein i l Retrovirus Generalites a simple linear genomic structure and survives in is host by suppressing the immune response to the virus The virus inhibits its host immune responses by using surface glycoprotein 70 and transmembrane anchor protein 15 Jarrett 1999 Both proteins are immunosuppressive agents and are coded by the env gene shown in this diagram and the table 1 Because this is a retrovirus it carries the enzyme reverse transcriptase By using the viral ribonucleic acid RNA as a template the reverse transcriptase is able to make a DNA copy of the template and integrate that strand into the genetic material of the infected host cell as a provirus Feline leukemia virus belongs to the former genus oncoviruses Recently this genus was reclassi ed by the lntemational Committee on the Taxonomy of Viruses into four distinct categories Feline leukemia ts into the category gammaretrovirus The genomic structure of this virus comprises 539 and 339 long terminal repeats LTR39s and three genes gag pol and am the total genome is about 9600 basepairs Jarrett 1999 Each gene encodes for a particular structure shown here Gene gag Function encodes the core proteins of the virion the MA matrix the CA capsid and the NC nucleocapsid encodes the enzymes concerned with replication and integration reverse transcriptase amp integrase encodes the glycoproteins of the envelope surface 39 39 SU amp protein TM The gene order looks like this S39cap gag pol env 339polyA ge Retrovirus structure neric Core Envelope Enzymes Structure amp Genomic Organization of FeLV amp other associated simple Retroviruses The infections of the four FeLV subgroups FeLV A B C and T are receptor specific Sampling and ampli cation of felid cDNA it was found that approximately 90 of the amino acid sequences identi ed share those sequences with human thiamine transport receptor 1 THTR l Mendoza 2006 This study was done to test FeLV to determine any possible transmission to humans All studies done involving zoonotic properties of the FeLV viral transmission to humans have been inconclusive Recent literature ndings From Principles of Virology Flint 2004 Endogenous FeLVs enFELV may anect the J 01 FeLVs Subgroup B FeLV a 39 39 between and J FeLVs may attenuate infection with the nonrecombinant virus On the other hand the recombinant subgroup C FeLV induces aplastic anemia in infected cats Also insertional polymorphisms in enFeLV may contribute to the development of feline cancer Roca 2005 Recently two endogenous feline leukemia viruses enFeLVAGTT and enFeLV GGAG were isolated and sequenced with prevalence of 89 and 152 respectively in a survey of domestic cats The two enFeLVs however were not found in the genomes of related species previously known to harbor enFeLVs The result indicates these enFeLVs are of recent origin and are replication competent Roca 2005 An llmonthold captivebred male neutered bobcat Felis rufus was diagnosed positive for feline leukemia virus The FeLV isolate s specific gag sequence was amplified by DNA polymerase chain reaction PCR and aligned with known domestic cat FeLV s The source of virus was suspected to be a domestic cat that was a surrogate nurse FeLV in nondomestic felids is rare Introduction of FeLV virus into freeliving populations could have serious consequences therefore measures to prevent the introduction of this virus to nondomestic felids are warranted Sleeman 2001 References amp Links Aiello Susan E et al The Merck Veterinary Manual 8Lh edition MERCK amp CO INC National Publishing Philadelphia 1998 Animal Health Channel Feline Leukemia Virus 2006 Cornell University College of Veterinary Medicine Feline Leukemia Virus 2006 httpwwwvetcornelledu Flint SJ et al Principles of Virology ASM Press Washington DC 2000 Harms Nicole Feline Leukemia Virus July 2006 httpwwwassociatedcontentcom Iyer D LeRoy B E and Latimer KS and Moore Feline leukemia virus infection 7 a review College of Veterinary Medicine University of Georgia Athens GA 2005 httpwwwvetugaedu Jarrett Oswald Strategies of retrovirus survival in the cat Veterinary Microbiology 1999 Keller Gomes Tandon R Gonczi E Meli ML HofmannLehmann R Lutz H Shedding of feline leukemia virus RNA in saliva is a consistent feature in viremic cats Veterinary Microbiology October 2005 Leukemia virus in a Captive Bobcat Journal of Wildlife Disease 37 194200 Mendoza R Maria M Anderson MM and Overbaugh J 2006 A putative thiamine transport protein is a receptor for feline leukemia virus subgroup A J Virol 80 33787 3385 Nash Holly Feline Leukemia Foster amp Smith Inc 1997 httpwwwpeteducationcomNational Center for Biotechnology Information NCBI August 1998 httpwwwncbinlmnihgov Paustian T Microbiology and Bacteriology The world of Microbes l9992006 httpwwwbactwiscedu Roca AL Nash WG Menninger JC Murphy WJ and SJ O Brien Insertional polymorphisms of endogenous feline leukemia viruses 2005 J Virol 2005 April 79 397973986 Roca AL PeconSlattery J and SJ O Brien Genomically Intact Endogenous Feline Leukemia Virus of Recent Origin J Virol 2005 April 78 43704375 Saidla John E and Jeffrey E Barlough Cornell Book of Cats November 2006 httpwwwvetcornelledufhc Sleeman JM Keane JM Johnson Brown RJ Sue Vande Woude 2001 Feline Steinberg Dr Dietrich Feline Leukemia Vet News amp Views 2004 httpwwwcreaturescom The Merck Veterinary Manual Feline Leukemia Virus and Related Diseases Introduction Feline lymphoma amp leukemia Lymphosarcoma Merck amp Co Inc 2006 httpWWWmerckvetmanualcom The Murray Lab Computational Biology Macromolecular interations in subcellular targeting http WWWmaatmedcomelleduretrovirusgammaFLVhtml Windy Hollow Veterinary Clinic Disease Information httpWWW 39 39 quot 39 39 VUtnu ou r html httpWWWWinnfelinehealthorg httpWWWVetcomelledu http WWWmerckvetmanual com I WWW orgWWW quot quot WWWanimalhealthchannelcom Picture references httpWWWapetsblogcom httpWWWsxchuphoto httpWWW 39 org cgi renrint 287 54591828pdf httpWWWlbahcomfelinefelVhtml hlIDIenwikinedin org WikiP 39 chain reaction
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