Journal
JOURNAL OF VIROLOGY
Volume 94, Issue 21, Pages -Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/JVI.01204-20
Keywords
Borna disease virus; endogenous bornavirus-like nucleoproteins; mathematical modeling; data analysis; endogenous bornavirus-like element
Categories
Funding
- AMED CREST [JP19gm1310002]
- AMED J-PRIDE [JP19fm0208006s0103, JP19fm0208014h, JP19fm0208019h0103]
- AMED Research Program on HIV/AIDS [JP19fk0410023s0101]
- Research Program on Emerging and Re-emerging Infectious Diseases [JP19fk0108050h0003]
- Program for Basic and Clinical Research on Hepatitis [JP19fk0210036h0502]
- Program on the Innovative Development and the Application of New Drugs for Hepatitis B [JP19fk0310114h0103]
- JSPS Core-to-Core Program, JST MIRAI
- JST CREST
- Mitsui Life Social Welfare Foundation
- Shin-Nihon of Advanced Medical Research
- Suzuken Memorial Foundation
- Life Science Foundation of Japan
- SECOM Science and Technology Foundation
- Japan Prize Foundation
- Toyota Physical and Chemical Research Institute
- National Research Foundation of Korea - Ministry of Education [2019R1A6A3A12031316]
- Shimizu Foundation for Immunology and Neuroscience
- Institute for Frontier Life and Medical Sciences, Kyoto University
- [JP18KT0018]
- [JP18H01139]
- [JP18H02664]
- [JP16H04845]
- [JP17H04083]
- [JP18K19449]
- [JP19K22530]
- [JP19H04839]
- [JP18H05103]
- [JP16H06429]
- [JP16K21723]
- [JP16H06430]
- National Research Foundation of Korea [2019R1A6A3A12031316] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Ask authors/readers for more resources
Endogenous retroviruses have demonstrated exaptation during long-term evolution with hosts, e.g., resulting in acquisition of antiviral effect on related extant viral infections. While empirical studies have found that an endogenous bornavirus-like element derived from viral nucleoprotein (itEBLN) in the ground squirrel genome shows antiviral effect on virus replication and de novo infection, the antiviral mechanism, dynamics, and quantitative effect of itEBLN remain unknown. In this study, we experimentally and theoretically investigated the dynamics of how an extant bornavirus, Borna disease virus 1 (BoDV-1), spreads and replicates in uninfected, BoDV-1-infected, and itEBLN-expressing cultured cells. Quantifying antiviral effect based on time course data sets, we found that the antiviral effects of itEBLN are estimated to be 75% and 34% on intercellular virus spread and intracellular virus replication, respectively. This discrepancy between intercellular virus spread and intracellular viral replication suggests that viral processes other than the replication of viral ribonucleoprotein complex (RNP) contributed to the suppression of virus spread in itEBLN-expressing cells. Because itEBLN binds to the BoDV-1 RNP, the suppression of viral RNP trafficking can be an attractive candidate explaining this discrepancy. IMPORTANCE Accumulating evidence suggests that some endogenous viral elements (EVEs), including endogenous retroviruses and endogenous nonretroviral virus elements, have acquired functions in the host as a result of long-term coevolution. Recently, an endogenous bornavirus-like element (itEBLN) found in the ground squirrel genome has been shown to have antiviral activity against exogenous bornavirus infection. In this study, we first quantified bornavirus spread in cultured cells and then calculated the antiviral activity of itEBLN on bornavirus infection. The calculated antiviral activity of itEBLN suggests its suppression of multiple processes in the viral life cycle. To our knowledge, this is the first study quantifying the antiviral activity of EVEs and speculating on a model of how some EVEs have acquired antiviral activity during host-virus arms races.
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