Riding apoptotic bodies for cell-cell transmission by African swine fever virus

African swine fever virus (ASFV), a devastating pathogen to the worldwide swine industry, mainly targets macrophage/monocyte lineage, but how the virus enters host cells has remained unclear. Here, we report that ASFV utilizes apoptotic bodies (ApoBDs) for infection and cell-cell transmission. We sh...

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Published in:Proceedings of the National Academy of Sciences - PNAS 2023-11, Vol.120 (48), p.e2309506120-e2309506120
Main Authors: Gao, Peng, Zhou, Lei, Wu, Jiajun, Weng, Wenlian, Wang, Hua, Ye, Miaomiao, Qu, Yajin, Hao, Yuxin, Zhang, Yongning, Ge, Xinna, Guo, Xin, Han, Jun, Yang, Hanchun
Format: Article
Language:English
Subjects:
African Swine Fever
African Swine Fever Virus - physiology
Alveoli
Animals
Annexin V
Antibodies
Apoptosis
Asfarviridae
Biological Sciences
Electron microscopy
Extracellular Vesicles - metabolism
Fever
Infections
Macrophages
Macrophages - metabolism
Membranes
Monocytes
Monocytes - metabolism
Secondary infection
Swine
Virions
Viruses
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Summary:African swine fever virus (ASFV), a devastating pathogen to the worldwide swine industry, mainly targets macrophage/monocyte lineage, but how the virus enters host cells has remained unclear. Here, we report that ASFV utilizes apoptotic bodies (ApoBDs) for infection and cell-cell transmission. We show that ASFV induces cell apoptosis of primary porcine alveolar macrophages (PAMs) at the late stage of infection to productively shed ApoBDs that are subsequently swallowed by neighboring PAMs to initiate a secondary infection as evidenced by electron microscopy and live-cell imaging. Interestingly, the virions loaded within ApoBDs are exclusively single-enveloped particles that are devoid of the outer layer of membrane and represent a predominant form produced during late infection. The in vitro purified ApoBD vesicles are capable of mediating virus infection of naive PAMs, but the transmission can be significantly inhibited by blocking the "eat-me" signal phosphatidyserine on the surface of ApoBDs via Annexin V or the efferocytosis receptor TIM4 on the recipient PAMs via anti-TIM4 antibody, whereas overexpression of TIM4 enhances virus infection. The same treatment however did not affect the infection by intracellular viruses. Importantly, the swine sera to ASFV exert no effect on the ApoBD-mediated transmission but can partially act on the virions lacking the outer layer of membrane. Thus, ASFV has evolved to hijack a normal cellular pathway for cell-cell spread to evade host responses.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.2309506120