Identification of AXL As a Co-receptor for Human Parvovirus B19 Infection of Human Erythroid Progenitors

Overview

Journal Sci Adv

Specialties Biology
Science

Date 2023 Jan 11

PMID 36630517

Authors

Kang Ning

Wei Zou

Peng Xu

Fang Cheng

Elizabeth Yan Zhang

Aaron Zhang-Chen

Steve Kleiboeker

Jianming Qiu

Affiliations

Soon will be listed here.

Abstract

Parvovirus B19 (B19V) infects human erythroid progenitor cells (EPCs) and causes several hematological disorders and fetal hydrops. Amino acid (aa) 5-68 of minor capsid protein VP1 (VP1u) is the minimal receptor binding domain for B19V to enter EPCs. Here, we carried out a genome-wide CRISPR-Cas9 guide RNA screen and identified tyrosine protein kinase receptor UFO (AXL) as a proteinaceous receptor for B19V infection of EPCs. gene silencing in ex vivo expanded EPCs remarkably decreased B19V internalization and replication. Additions of the recombinant AXL extracellular domain or a polyclonal antibody against it upon infection efficiently inhibited B19V infection of ex vivo expanded EPCs. Moreover, B19V VP1u interacted with the recombinant AXL extracellular domain in vitro at a relatively high affinity ( = 103 nM). Collectively, we provide evidence that AXL is a co-receptor for B19V infection of EPCs.

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References

Kronenberg S, Bottcher B, von der Lieth C, Bleker S, Kleinschmidt J . A conformational change in the adeno-associated virus type 2 capsid leads to the exposure of hidden VP1 N termini. J Virol. 2005; 79(9):5296-303. PMC: 1082756. DOI: 10.1128/JVI.79.9.5296-5303.2005. View

Kajigaya S, Fujii H, Field A, Anderson S, Rosenfeld S, Anderson L . Self-assembled B19 parvovirus capsids, produced in a baculovirus system, are antigenically and immunogenically similar to native virions. Proc Natl Acad Sci U S A. 1991; 88(11):4646-50. PMC: 51722. DOI: 10.1073/pnas.88.11.4646. View

Riipinen A, Vaisanen E, Nuutila M, Sallmen M, Karikoski R, Lindbohm M . Parvovirus b19 infection in fetal deaths. Clin Infect Dis. 2008; 47(12):1519-25. DOI: 10.1086/593190. View

Serjeant G, Topley J, Mason K, Serjeant B, Pattison J, Jones S . Outbreak of aplastic crises in sickle cell anaemia associated with parvovirus-like agent. Lancet. 1981; 2(8247):595-7. DOI: 10.1016/s0140-6736(81)92739-2. View

Gigler A, Dorsch S, Hemauer A, Williams C, Kim S, Young N . Generation of neutralizing human monoclonal antibodies against parvovirus B19 proteins. J Virol. 1999; 73(3):1974-9. PMC: 104439. DOI: 10.1128/JVI.73.3.1974-1979.1999. View

Cotmore S, McKie V, Anderson L, Astell C, Tattersall P . Identification of the major structural and nonstructural proteins encoded by human parvovirus B19 and mapping of their genes by procaryotic expression of isolated genomic fragments. J Virol. 1986; 60(2):548-57. PMC: 288924. DOI: 10.1128/JVI.60.2.548-557.1986. View

Ning K, Wang Z, Cheng F, Yan Z, Qiu J . The small nonstructural protein NP1 of human bocavirus 1 directly interacts with Ku70 and RPA70 and facilitates viral DNA replication. PLoS Pathog. 2022; 18(6):e1010578. PMC: 9197078. DOI: 10.1371/journal.ppat.1010578. View

Kurtzman G, Frickhofen N, Kimball J, JENKINS D, Nienhuis A, Young N . Pure red-cell aplasia of 10 years' duration due to persistent parvovirus B19 infection and its cure with immunoglobulin therapy. N Engl J Med. 1989; 321(8):519-23. DOI: 10.1056/NEJM198908243210807. View

Bieri J, Leisi R, Bircher C, Ros C . Human parvovirus B19 interacts with globoside under acidic conditions as an essential step in endocytic trafficking. PLoS Pathog. 2021; 17(4):e1009434. PMC: 8087101. DOI: 10.1371/journal.ppat.1009434. View

10.

Luo Y, Lou S, Deng X, Liu Z, Li Y, Kleiboeker S . Parvovirus B19 infection of human primary erythroid progenitor cells triggers ATR-Chk1 signaling, which promotes B19 virus replication. J Virol. 2011; 85(16):8046-55. PMC: 3147961. DOI: 10.1128/JVI.00831-11. View

11.

Pillay S, Meyer N, Puschnik A, Davulcu O, Diep J, Ishikawa Y . An essential receptor for adeno-associated virus infection. Nature. 2016; 530(7588):108-12. PMC: 4962915. DOI: 10.1038/nature16465. View

12.

Wang S, Qiu Z, Hou Y, Deng X, Xu W, Zheng T . AXL is a candidate receptor for SARS-CoV-2 that promotes infection of pulmonary and bronchial epithelial cells. Cell Res. 2021; 31(2):126-140. PMC: 7791157. DOI: 10.1038/s41422-020-00460-y. View

13.

Ma W, Yang L, He L . Overview of the detection methods for equilibrium dissociation constant of drug-receptor interaction. J Pharm Anal. 2018; 8(3):147-152. PMC: 6004624. DOI: 10.1016/j.jpha.2018.05.001. View

14.

Shimojima M, Ikeda Y, Kawaoka Y . The mechanism of Axl-mediated Ebola virus infection. J Infect Dis. 2007; 196 Suppl 2:S259-63. DOI: 10.1086/520594. View

15.

Zou W, Wang Z, Xiong M, Chen A, Xu P, Ganaie S . Human Parvovirus B19 Utilizes Cellular DNA Replication Machinery for Viral DNA Replication. J Virol. 2017; 92(5). PMC: 5809726. DOI: 10.1128/JVI.01881-17. View

16.

Anderson S, Momoeda M, Kawase M, Kajigaya S, Young N . Peptides derived from the unique region of B19 parvovirus minor capsid protein elicit neutralizing antibodies in rabbits. Virology. 1995; 206(1):626-32. DOI: 10.1016/s0042-6822(95)80079-4. View

17.

Anderson M, Higgins P, Davis L, Willman J, Jones S, Kidd I . Experimental parvoviral infection in humans. J Infect Dis. 1985; 152(2):257-65. DOI: 10.1093/infdis/152.2.257. View

18.

Guan W, Cheng F, Yoto Y, Kleiboeker S, Wong S, Zhi N . Block to the production of full-length B19 virus transcripts by internal polyadenylation is overcome by replication of the viral genome. J Virol. 2008; 82(20):9951-63. PMC: 2566258. DOI: 10.1128/JVI.01162-08. View

19.

Bieri J, Ros C . Globoside Is Dispensable for Parvovirus B19 Entry but Essential at a Postentry Step for Productive Infection. J Virol. 2019; 93(20). PMC: 6798098. DOI: 10.1128/JVI.00972-19. View

20.

Wong S, Zhi N, Filippone C, Keyvanfar K, Kajigaya S, Brown K . Ex vivo-generated CD36+ erythroid progenitors are highly permissive to human parvovirus B19 replication. J Virol. 2007; 82(5):2470-6. PMC: 2258946. DOI: 10.1128/JVI.02247-07. View