Complete Genome Sequences of Two Feline Leukemia Virus Subgroup B Isolates with Novel Recombination Sites

Stewart, Hazel; Jarrett, Oswald; Hosie, Margaret J.; Willett, Brian J.

doi:10.1128/genomea.00036-12

Cited by 13 publications

(10 citation statements)

References 12 publications

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“…FeLV-B infection has been associated with leukemia, lymphoma, and increased pathogenesis (17). FeLV-B is nearly always identified in the presence of FeLV-A and is not typically horizontally transmissible in the absence of FeLV-A (17)(18)(19)(20), although there has been in vitro evidence that FeLV-B can be isolated without FeLV-A being present (66). FeLV-A has been determined to use the thiamine transport protein (feTHTR1) as a cell entry receptor, whereas FeLV-B uses inorganic phosphate transporters Pit1 and Pit2 as receptors to gain cell entry (67).…”

Section: Figmentioning

confidence: 99%

Feline Leukemia Virus (FeLV) Disease Outcomes in a Domestic Cat Breeding Colony: Relationship to Endogenous FeLV and Other Chronic Viral Infections

Powers

Chiu

Kraberger

et al. 2018

J Virol

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Exogenous feline leukemia virus (FeLV) is a feline gammaretrovirus that results in a variety of disease outcomes. Endogenous FeLV (enFeLV) is a replication-defective provirus found in species belonging to the genus, which includes the domestic cat (). There have been few studies examining interaction between enFeLV genotype and FeLV progression. We examined point-in-time enFeLV and FeLV viral loads, as well as occurrence of FeLV/enFeLV recombinants (FeLV-B), to determine factors relating to clinical disease in a closed breeding colony of cats during a natural infection of FeLV. Coinfections with feline foamy virus (FFV), feline gammaherpesvirus 1 (FcaGHV-1), and feline coronavirus (FCoV) were also documented and analyzed for impact on cat health and FeLV disease. Correlation analysis and structural equation modeling techniques were used to measure interactions among disease parameters. Progressive FeLV disease and FeLV-B presence were associated with higher FeLV proviral and plasma viral loads. Female cats were more likely to have progressive disease and FeLV-B. Conversely, enFeLV copy number was higher in male cats and negatively associated with progressive FeLV disease. Males were more likely to have abortive FeLV disease. FFV proviral load was found to correlate positively with higher FeLV proviral and plasma viral load, detection of FeLV-B, and FCoV status. Male cats were much more likely to be infected with FcaGHV-1 than female cats. This analysis provides insights into the interplay between endogenous and exogenous FeLV during naturally occurring disease and reveals striking variation in the infection patterns among four chronic viral infections of domestic cats. Endogenous retroviruses are harbored by many animals, and their interactions with exogenous retroviral infections have not been widely studied. Feline leukemia virus (FeLV) is a relevant model system to examine this question, as endogenous and exogenous forms of the virus exist. In this analysis of a large domestic cat breeding colony naturally infected with FeLV, we documented that enFeLV copy number was higher in males and inversely related to FeLV viral load and associated with better FeLV disease outcomes. Females had lower enFeLV copy numbers and were more likely to have progressive FeLV disease and FeLV-B subtypes. FFV viral load was correlated with FeLV progression. FFV, FcaGHV-1, and FeLV displayed markedly different patterns of infection with respect to host demographics. This investigation revealed complex coinfection outcomes and viral ecology of chronic infections in a closed population.

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Section: Figmentioning

confidence: 99%

Feline Leukemia Virus (FeLV) Disease Outcomes in a Domestic Cat Breeding Colony: Relationship to Endogenous FeLV and Other Chronic Viral Infections

Powers

Chiu

Kraberger

et al. 2018

J Virol

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“…Virulent FeLV-B, the most common novel variant, arises after recombination between FeLV-A and endogenous FeLV (EnFeLV) present in the domestic cat genome and resulted in altered cellular tropism ( 1 , 7 – 10 ). Horizontal transmission of FeLV-B is rare in domestic cats and is believed to require co-transmission with FeLV-A as a helper virus because of its replication-defective nature ( 11 , 12 ).…”

mentioning

confidence: 99%

“…The genus Felis is the only taxon known to harbor enFeLV ( 22 ). The presence of FeLV genetic sequences in the germline results in recombination between exogenous FeLV and FeLV-A during domestic cat infections and in emergence of more deleterious subgroups (i.e., FeLV-B) that are not considered to be replication-competent in the absence of co-infection with FeLV-A ( 12 ). It is assumed that felids belonging to genera other than Felis are only infected with FeLV-A because they do not harbor enFeLV genomes.…”

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confidence: 99%

Multiple Introductions of Domestic Cat Feline Leukemia Virus in Endangered Florida Panthers1

Chiu¹,

Kraberger²,

Cunningham³

et al. 2019

Emerg. Infect. Dis.

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The endangered Florida panther (Puma concolor coryi) had an outbreak of infection with feline leukemia virus (FeLV) in the early 2000s that resulted in the deaths of 3 animals. A vaccination campaign was instituted during 2003–2007 and no additional cases were recorded until 2010. During 2010–2016, six additional FeLV cases were documented. We characterized FeLV genomes isolated from Florida panthers from both outbreaks and compared them with full-length genomes of FeLVs isolated from contemporary Florida domestic cats. Phylogenetic analyses identified at least 2 circulating FeLV strains in panthers, which represent separate introductions from domestic cats. The original FeLV virus outbreak strain is either still circulating or another domestic cat transmission event has occurred with a closely related variant. We also report a case of a cross-species transmission event of an oncogenic FeLV recombinant (FeLV-B). Evidence of multiple FeLV strains and detection of FeLV-B indicate Florida panthers are at high risk for FeLV infection.

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“…Cells infected with a retrovirus in any tissue could express viral antigen without producing infectious particles that could stimulate an antibody response; serological reactivity could also be targeted to aberrant expression of a HERV-K [25]. Given the well-established potential of infectious retroviruses to activate and recombine with ERVs [30, 41–46], an additional and intriguing consideration is that a chimeric, replication-incompetent retrovirus exists in LGL leukemia patients. These possibilities may be investigated by further immunological analyses to understand the nature of the antigens that can either induce an anti-retroviral response or sustain proliferation of LGL or both.…”

Section: Discussionmentioning

confidence: 99%

Retrovirus insertion site analysis of LGL leukemia patient genomes

Yang

Harris

et al. 2019

Preprint

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23Background: Large granular lymphocyte (LGL) leukemia is an uncommon cancer characterized 24 by a sustained clonal proliferation of LGL cells. Antibodies reactive to retroviruses have been 25 documented in the serum of patients with LGL leukemia. Culture or molecular approaches have 26 to date not been successful in identifying a retrovirus. 27 Methods: Because a retrovirus must integrate into the genome of an infected cell, we focused 28 our efforts on detecting a novel retrovirus integration site in the clonally expanded LGL cells. 29We present a new computational tool that uses long-insert mate pair sequence data to search the 30 genome of LGL leukemia cells for retrovirus integration sites. We also utilize recently published 31 methods to interrogate the status of polymorphic human endogenous retrovirus type K (HERV-K) 32 provirus in patient genomes. 33Results: While our analysis did not reveal any new retrovirus insertions in LGL genomes from 34LGL leukemia patients, we did identify four HERV-K provirus integration sites that are 35 polymorphic in the human population and absent from the human reference genome, hg19. To 36 determine if the prevalence of these or other polymorphic proviral HERV-Ks differed between 37LGL leukemia patients and the general population, we applied a recently developed approach 38 that reports all sites in the human genome occupied by a proviral HERV-K. Using the 1000 39 genomes project (KGP) data as a reference database for HERV-K proviral prevalence at each 40 polymorphic site, we show that there are significant differences in the number of polymorphic 41 HERV-Ks in the genomes of LGL leukemia patients of European origin compared to individuals 42 with European ancestry in the KGP data. 43 Conclusions:Our study confirms that the integration of a new infectious or endogenous 44 retrovirus does not cause the clonal expansion of LGL cells in LGL leukemia, although we do 45 3 not rule out that these cells could be responding to retroviral antigens produced in other cell 46 types. However, it is of interest that the burden of polymorphic proviral HERV-K is elevated in 47LGL leukemia patient genomes. Our research emphasizes the merits of comprehensive genomic 48 assessment of HERV-K in cancer samples and suggests that further analyses to determine 49 contributions of HERV-K to LGL leukemia are warranted. 50 Keywords: Large granular lymphocyte leukemia, retrovirus, HERV-K, genomic insertion, 51 visualization tool 52 53 Background 54 Large granular lymphocyte (LGL) leukemia is a rare, chronic, proliferative disorder of cytotoxic 55 T cells (approximately 85% of cases) and NK cells [1]. Diagnosis of this leukemia is based on a 56 sustained elevation of a clonally expanded T or NK cell population. LGL leukemia is reported 57 most frequently in patients from North America and Europe and up to half of patients also have 58 an autoimmune disorder, most frequently rheumatoid arthritis [2]. A small subset of patients 59 show clonal proliferation of CD4+ cells, which has been associated with Cy...

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Complete Genome Sequences of Two Feline Leukemia Virus Subgroup B Isolates with Novel Recombination Sites

Cited by 13 publications

References 12 publications

Feline Leukemia Virus (FeLV) Disease Outcomes in a Domestic Cat Breeding Colony: Relationship to Endogenous FeLV and Other Chronic Viral Infections

Feline Leukemia Virus (FeLV) Disease Outcomes in a Domestic Cat Breeding Colony: Relationship to Endogenous FeLV and Other Chronic Viral Infections

Multiple Introductions of Domestic Cat Feline Leukemia Virus in Endangered Florida Panthers1

Retrovirus insertion site analysis of LGL leukemia patient genomes

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