Genetic diversity in the feline leukemia virus gag gene

Kawamura, Morio; Watanabe, Shinya; Odahara, Yuka; Nakagawa, So; Endo, Yasuyuki; Tsujimoto, Hajime; Nishigaki, Kazuo

doi:10.1016/j.virusres.2015.04.008

Cited by 10 publications

(9 citation statements)

References 62 publications

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“…FeLV is transmitted among domestic cats at high prevalence in Japan and shows high genetic diversity due to the mutation or recombination of viral genes (5,50). Mutation of the FeLV Env sequence, especially in the VRA, may lead to a change in the viral receptor interference group.…”

Section: Discussionmentioning

confidence: 99%

Reduced Folate Carrier: an Entry Receptor for a Novel Feline Leukemia Virus Variant

Miyake

Kawasaki

Ngo

et al. 2019

J Virol

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Feline leukemia virus (FeLV) is horizontally transmitted among cats and causes a variety of hematopoietic disorders. Five subgroups of FeLV, A to D and T, each with distinct receptor usages, have been described. Recently, we identified a new FeLV Env (TG35-2) gene from a pseudotyped virus that does not belong to any known subgroup. FeLV-A is the primary virus from which other subgroups have emerged via mutation or recombination of the subgroup Aenvgene. Retrovirus entry into cells is mediated by the interaction of envelope protein (Env) with specific cell surface receptors. Here, phenotypic screening of a human/hamster radiation hybrid panel identified SLC19A1, a feline reduced folate carrier (RFC) and potential receptor for TG35-2-phenotypic virus. RFC is a multipass transmembrane protein. Feline and human RFC cDNAs conferred susceptibility to TG35-2-pseudotyped virus when introduced into nonpermissive cells but did not render these cells permissive to other FeLV subgroups or feline endogenous retrovirus. Moreover, human cells with genomic deletion of RFC were nonpermissive for TG35-2-pseudotyped virus infection, but the introduction of feline and human cDNAs rendered them permissive. Mutation analysis of FeLV Env demonstrated that amino acid substitutions within variable region A altered the specificity of the Env-receptor interaction. We isolated and reconstructed the full-length infectious TG35-2-phenotypic provirus from a naturally FeLV-infected cat, from which the FeLV Env (TG35-2) gene was previously isolated, and compared the replication of the virus in hematopoietic cell lines with that of FeLV-A 61E by measuring the viral RNA copy numbers. These results provide a tool for further investigation of FeLV infectious disease.IMPORTANCEFeline leukemia virus (FeLV) is a member of the genusGammaretrovirus, which causes malignant diseases in cats. The most prevalent FeLV among cats is FeLV subgroup A (FeLV-A), and specific binding of FeLV-A Env to its viral receptor, thiamine transporter feTHTR1, is the first step of infection. In infected cats, novel variants of FeLV with altered receptor specificity for viral entry have emerged by mutation or recombination of theenvgene. A novel FeLV variant arose from a subtle mutation of FeLV-A Env, which altered the specific interaction of the virus with its receptor. RFC, a folate transporter, is a potential receptor for the novel FeLV variant. The perturbation of specific retrovirus-receptor interactions under selective pressure by the host results in the emergence of novel viruses.

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Section: Discussionmentioning

confidence: 99%

Reduced Folate Carrier: an Entry Receptor for a Novel Feline Leukemia Virus Variant

Miyake

Kawasaki

Ngo

et al. 2019

J Virol

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“…Isolation of a recombinant FeLV gag gene. The specific PCR method used for surveying the exogenous FeLV gag gene was previously established; it uses primers Fe-23S and Fe-48R corresponding to the 5= LTR and the pol gene, respectively, and can detect the entire 2.3-kbp FeLV gag gene (86). We conducted PCR on our FeLV-positive samples, and the resulting fragments were each cloned into a pCR-4Blunt-TOPO vector (Invitrogen).…”

Section: Methodsmentioning

confidence: 99%

Presence of a Shared 5′-Leader Sequence in Ancestral Human and Mammalian Retroviruses and Its Transduction into Feline Leukemia Virus

Kawasaki

Kawamura

Ohsato³

et al. 2017

J Virol

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Recombination events induce significant genetic changes, and this process can result in virus genetic diversity or in the generation of novel pathogenicity. We discovered a new recombinant feline leukemia virus (FeLV) gene harboring an unrelated insertion, termed the X region, which was derived from endogenous gammaretrovirus 4 (FcERV-gamma4). The identified FcERV-gamma4 proviruses have lost their coding capabilities, but some can express their viral RNA in feline tissues. Although the X-region-carrying recombinant FeLVs appeared to be replication-defective viruses, they were detected in 6.4% of tested FeLV-infected cats. All isolated recombinant FeLV clones commonly incorporated a middle part of the FcERV-gamma4 5'-leader region as an X region. Surprisingly, a sequence corresponding to the portion contained in all X regions is also present in at least 13 endogenous retroviruses (ERVs) observed in the cat, human, primate, and pig genomes. We termed this shared genetic feature the commonly shared (CS) sequence. Despite our phylogenetic analysis indicating that all CS-sequence-carrying ERVs are classified as gammaretroviruses, no obvious closeness was revealed among these ERVs. However, the Shannon entropy in the CS sequence was lower than that in other parts of the provirus genome. Notably, the CS sequence of human endogenous retrovirus T had 73.8% similarity with that of FcERV-gamma4, and specific signals were detected in the human genome by Southern blot analysis using a probe for the FcERV-gamma4 CS sequence. Our results provide an interesting evolutionary history for CS-sequence circulation among several distinct ancestral viruses and a novel recombined virus over a prolonged period. Recombination among ERVs or modern viral genomes causes a rapid evolution of retroviruses, and this phenomenon can result in the serious situation of viral disease reemergence. We identified a novel recombinant FeLV gene that contains an unrelated sequence, termed the X region. This region originated from the 5' leader of FcERV-gamma4, a replication-incompetent feline ERV. Surprisingly, a sequence corresponding to the X region is also present in the 5' portion of other ERVs, including human endogenous retroviruses. Scattered copies of the ERVs carrying the unique genetic feature, here named the commonly shared (CS) sequence, were found in each host genome, suggesting that ancestral viruses may have captured and maintained the CS sequence. More recently, a novel recombinant FeLV hijacked the CS sequence from inactivated FcERV-gamma4 as the X region. Therefore, tracing the CS sequences can provide unique models for not only the modern reservoir of new recombinant viruses but also the genetic features shared among ancient retroviruses.

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“…We then investigated FeLV infection rates in TLCs (90 cats in total) collected between 1999 and 2014. The majority of TLCs had been hit by vehicles (road kills), and FeLV infections were detected with a blood test (SNAP FeLV/FIV combo kit, IDEXX Laboratories) and PCR 12,27 using the chromosomal DNA from blood, spleen, and kidney samples. No FeLV antigen or gag or env gene was detected in any TLC sample with the commercial kit or PCR.…”

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confidence: 99%

“…3A). PCR primers Fe-23S and Fe-48R (Supplementary Table 1) amplified a fragment of ~2.4 kb (i.e., the entire FeLV gag gene) 12 from the TLC skin fibroblasts infected with FeLV-A/clone 33 or FeLV-B/ Gardner-Arnstein, but not from uninfected TLC skin fibro-blasts ( Fig. 3B).…”

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Epidemiologic survey of feline leukemia virus in domestic cats on Tsushima Island, Japan: management strategy for Tsushima leopard cats

et al. 2017

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The Tsushima leopard cat (TLC) Prionailurus bengalensis euptilurus, a subspecies of P. bengalensis, is designated a National Natural Monument of Japan, and lives only on Tsushima Island, Nagasaki Prefecture, Japan. TLCs are threatened by various infectious diseases. Feline leukemia virus (FeLV) causes a serious infectious disease with a poor prognosis in cats. Therefore, the transmission of FeLV from Tsushima domestic cats (TDCs) to TLCs may threaten the TLC population. We investigated the FeLV infection status of both TDCs and TLCs on Tsushima Island by screening blood samples for FeLV p27 antigen and using PCR to amplify the full-length FeLV env gene. The prevalence of FeLV was 6.4% in TDCs and 0% in TLCs. We also demonstrated that the virus can replicate in the cells of TLCs, suggesting its potential cross-species transmission. The viruses in TDCs were classified as genotype I/clade 3, which is prevalent on a nearby island, based on previous studies of FeLV genotypes and FeLV epidemiology. The FeLV viruses identified on Tsushima Island can be further divided into 2 lineages within genotype I/clade 3, which are geographically separated in Kamijima and Shimojima, indicating that FeLV may have been transmitted to Tsushima Island at least twice. Monitoring FeLV infection in the TDC and TLC populations is highly recommended as part of the TLC surveillance and management strategy.

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Genetic diversity in the feline leukemia virus gag gene

Cited by 10 publications

References 62 publications

Reduced Folate Carrier: an Entry Receptor for a Novel Feline Leukemia Virus Variant

Reduced Folate Carrier: an Entry Receptor for a Novel Feline Leukemia Virus Variant

Presence of a Shared 5′-Leader Sequence in Ancestral Human and Mammalian Retroviruses and Its Transduction into Feline Leukemia Virus

Epidemiologic survey of feline leukemia virus in domestic cats on Tsushima Island, Japan: management strategy for Tsushima leopard cats

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