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Refrex-1, a soluble restriction factor against feline endogenous and exogenous retroviruses
Jumpei Ito1, Shinya Watanabe, Takahiro Hiratsuka
1Laboratory of Molecular Immunology and Infectious Disease, Joint Faculty of Veterinary Medicine.
Abstract:
The host defense against viral infection is acquired during the coevolution or symbiosis of the host and pathogen. Several cellular factors that restrict retroviral infection have been identified in the hosts. Feline leukemia virus (FeLV) is a gammaretrovirus that is classified into several receptor interference groups, including a novel FeLV-subgroup D (FeLV-D) that we recently identified. FeLV-D is generated by transduction of the env gene of feline endogenous gammaretrovirus of the domestic cat (ERV-DCs) into FeLV. Some ERV-DCs are replication competent viruses which are present and hereditary in cats. We report here the determination of new viral receptor interference groups and the discovery of a soluble antiretroviral factor, termed Refrex-1. Detailed analysis of FeLV-D strains and ERV-DCs showed two receptor interference groups that are distinct from other FeLV subgroups, and Refrex-1 specifically inhibited one of them. Refrex-1 is characterized as a truncated envelope protein of ERV-DC and includes the N-terminal region of surface unit, which is a putative receptor-binding domain, but lacks the transmembrane region. Refrex-1 is efficiently secreted from the cells and appears to cause receptor interference extracellularly. Two variants of Refrex-1 encoded by provirus loci, ERV-DC7 and DC16, are expressed in a broad range of feline tissues. The host retains Refrex-1 as an antiretroviral factor, which may potentially prevent reemergence of the ERVs and the emergence of novel ERV-related viruses in cats. Refrex-1 may have been acquired during endogenization of ERV-DCs and may play an important role in retroviral restriction and antiviral defense in cats.
Insights
Researchers discovered Refrex-1, a soluble antiretroviral factor in cats, which inhibits specific feline endogenous gammaretroviruses (ERV-DCs) and novel FeLV-D strains. This factor may be crucial for feline antiviral defense.
Area of Science:
- Virology
- Immunology
- Genetics
Background:
- Host defense against viral infections involves coevolution with pathogens.
- Cellular factors restricting retroviral infections are known in hosts.
- Feline endogenous gammaretroviruses (ERV-DCs) are hereditary in cats and can be replication-competent.
Purpose of the Study:
- To identify new viral receptor interference groups for feline leukemia virus (FeLV).
- To discover novel antiretroviral factors involved in feline host defense.
- To characterize the mechanism of action and expression of these factors.
Main Methods:
- Analysis of FeLV-D strains and ERV-DCs to determine receptor interference groups.
- Characterization of Refrex-1 as a truncated envelope protein of ERV-DC.
- Investigation of Refrex-1 secretion and its effect on receptor interference.
- Analysis of Refrex-1 variants encoded by provirus loci (ERV-DC7, DC16) in feline tissues.
Main Results:
- Two new viral receptor interference groups distinct from other FeLV subgroups were identified.
- A soluble antiretroviral factor, Refrex-1, was discovered and specifically inhibited one of these groups.
- Refrex-1 is a secreted, truncated ERV-DC envelope protein that acts extracellularly.
- Two Refrex-1 variants are expressed in various feline tissues.
Conclusions:
- Refrex-1 acts as a soluble antiretroviral factor in cats, potentially preventing the reemergence of ERVs.
- This factor may play a significant role in retroviral restriction and antiviral defense in the feline host.
- Refrex-1 might have been acquired during the endogenization of ERV-DCs, contributing to long-term host defense.
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