FeLIX is a restriction factor against mammalian retrovirus infections

A research group led by Professor Kazuo Nishigaki at the Laboratory of MolecularImmunology and Infectious Disease (Joint Graduate School of Veterinary Medicine,Yamaguchi University) recently identified a secreted protein that blocks various retrovirus
infections, including those caused by the feline leukemia virus (FeLV), in domestic cats. The
results of this study can facilitate the development of new prevention and treatment methods
for infectious diseases.
FeLV is a retrovirus that causes anemia and hematopoietic diseases, such as lymphoma andleukemia, in domestic cats (Felis catus). This virus infects animals by binding to the entry
receptor on the cell surface. Notably, different FeLV subgroups use different entry receptors.
For example, the entry receptor for FeLV-A is THTR1, a vitamin B1 transporter, whereas thatfor FeLV-B is Pit, a phosphate transporter.
FeLV-A is transmitted among domestic cats. Interestingly, FeLV-A infection leads to viral generecombination in domestic cats, resulting in the emergence of a new virus, FeLV-B. UnlikeFeLV-A, FeLV-B is not transmitted among domestic cats. In this study, we investigated themechanism responsible for this difference in the transmission of different viruses. Genomes
analysis revealed that the secreted protein, FeLIX, blocked the transmission of FeLV-B among
domestic cats.
FeLIX is encoded by an endogenous retrovirus, known as the ancient virus (footnote 1), andderived from its envelope gene. Genetic analysis revealed that FeLIX was derived from theancient virus infecting the domestic cat ancestors approximately 700,000 years ago. Inaddition to domestic cats, FeLIX has been detected in the European wild cats (F. silvestris).
Our findings revealed that FeLIX prevented FeLV-B infection by masking its entry receptor.
FeLIX is a secreted protein released by lymphocytes that circulates in the blood of domesticcats and inhibits the cellular entry of viruses. Additionally, we observed retroviruses similar toFeLV-B in several animal species, including gibbons, bats, and koalas. Notably, FeLIX also
inhibited the infections caused by these viruses. These findings suggest that FeLIX protects
domestic cats against various retroviruses by acting as a restriction factor. The results of thisstudy were published on March 05, 2024 in the Journal of Virology, American Society forMicrobiology.
Footnote 1. Endogenous retroviruses. Genome retains the sequences of all retroviruses that
previously infected the host. Endogenous retroviral sequences account for approximately 8%of the human genome.

【Information on published papers】
Title

FeLIX is a restriction factor against mammalian retrovirus infections
Authors
Didik Pramono, Dai Takeuchi, Masato Kouki, Loai AbuEed, Dimas Abdillah, Tohru Kimura,
Junna Kawasaki, Ariko Miyake, and Kazuo Nishigaki
Affiliation

Laboratory of Molecular Immunology and Infectious Disease, Joint Graduate School ofVeterinary Medicine, Yamaguchi University (Didik Pramono, Dai Takeuchi, Masato Kouki,
Loai AbuEed, Dimas Abdillah, Ariko Miyake, Kazuo Nishigaki)
Joint Graduate School of Veterinary Medicine, Yamaguchi University (Tohru Kimura)
Faculty of Science and Engineering Research Institute, Waseda University (Junna Kawasaki)
JournalJournal of Virology
DOI: https://doi.org/10.1128/jvi.01771-23
Contact

Laboratory of Molecular Immunology and Infectious Disease, Joint Faculty of Veterinary
Medicine, Yamaguchi University
Professor Kazuo Nishigaki
E-mail: kaz@yamaguchi-u.ac.jp
Acknowledgments

This work was supported by the Japan Society for the Promotion of Science (KAKENHI).
Principal Investigator: Kazuo Nishigaki
Research Grant Number: 20H03152 and 23H0239

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Figure Description: The domestic cat has a secreted protein, FeLIX, derived from endogenous retroviruses,
which is suggested to block the spread of retroviruses (GaLV, HPG, KoRV-A, FeLV-B) in various animals.
(Pictures were designed by Miyu Tanaka, a veterinarian; graduated from the Joint Faculty of Veterinary
Medicine, Yamaguchi University in March 2023)