2021–2023
Major Research Plan of the National Natural Science Foundation of ChinaProject title: The mechanism of host cell lysis by archaeal viruses in extreme environments and its phylogenetic and ecological distributionRole: Task leader
Archaeal viruses from acidic hot springs
Viral Infection Strategies under Extreme Environments
During my Ph.D. study at the Institute of Microbiology, Chinese Academy of Sciences (IMCAS), I investigated virus-host interactions in acidic hot springs in Costa Rica, focusing on a central question: What infection strategies enable viruses to maintain structural integrity and successfully propagate under extreme acidothermal conditions (pH 2–3, 86–106 °C)? Starting from hot spring sediments, I established an interaction system between Sulfolobus sp. A20 and an enveloped archaeal virus, Sulfolobus ellipsoid virus 1 (SEV1). By integrating cryo-electron tomography (cryo-ET), cryo-focused ion beam (cryo-FIB) milling, and subtomogram averaging (STA), I obtained the following findings: (1) A “coiling-stacking” genome-packaging model for SEV1. I proposed that a single major capsid protein binds viral DNA to form nucleoprotein filaments like “beads-on-a-string”, which then coil and stack layer by layer to build the nucleocapsid. Homologs of this protein are distributed across hot springs worldwide and deep-sea environments, suggesting a conserved strategy for protecting genetic material under extreme conditions. (2) A structural adaptation mechanism combining a flexible nucleocapsid with envelope-mediated stability. In contrast to many extremophilic viruses that rely on rigid architectures for stability, SEV1 displays a highly flexible nucleocapsid, whereas the envelope plays a decisive role in maintaining structural stability. (3) An integrated picture of the entire infection cycle of SEV1 in its native state. I captured the full process of virion maturation within the host cytoplasm and progeny release through hexagonal pyramidal openings, leaving behind ghost cells. These observations revealed a distinctive assembly and egress route for enveloped archaeal viruses.
Collectively, this work elucidated the structural stability and infection strategies that SEV1 has evolved for survival in extreme acidothermal environments, expanding our understanding of life processes in extreme environments.
This research was supported by a seed grant under the NSFC Major Research Program “Mechanisms of Aquatic Microorganisms Driving Earth's Elemental Cycles”. The results were published in Journal of Virology (Featured Article; co-first author) and Science Advances (co-first author and corresponding author). These studies established my research foundation in viral structural biology and in developing virus-host interaction systems for mechanistic dissection of infection processes.
In the publication lists below, * co-first author, # corresponding author.
SEV1, Sulfolobus ellipsoid virus 1
- Zhang H*, Wang H*#, Li Y, Fan Y, Zhang Z, Chen H, Song K, Huang L#, Zhu P#. (2025). Insights into the spool-like architecture and infection strategy of an enveloped archaeal virus. Science Advances, 11(29): eadv7326.
- Wang H*, Guo Z*, Feng H, Chen Y, Chen X, Li Z, Hernández-Ascencio W, Dai X, Zhang Z, Zheng X, Mora-López M, Fu Y, Zhang C, Zhu P#, Huang L#. (2018). Novel Sulfolobus virus with an exceptional capsid architecture. Journal of Virology, 92(5): e01727-17.
- Huang L#, Wang H, ICTV Report Consortium. (2021). ICTV Virus Taxonomy Profile: Ovaliviridae. Journal of General Virology, 102(3): 001546.
- Dai X, Wang H, Zhang Z, Li K, Zhang X, Mora-López M, Jiang C, Liu C, Wang L, Zhu Y, Hernández-Ascencio W, Dong Z, Huang L#. (2016). Genome sequencing of Sulfolobus sp. A20 from Costa Rica and comparative analyses of the putative pathways of carbon, nitrogen, and sulfur metabolism in various Sulfolobus strains. Frontiers in Microbiology, 7: 1902.
Doctoral thesis (2017): Isolation and characterization of Sulfolobus ellipsoid virus 1 (SEV1) from a hot spring in Costa Rica
Protein self-assembly
- Song L*, Wang H*, Wang S, Zhang H, Cong H, Huang L#, Tien P#. (2014). Self-assembled bionanoparticles based on the Sulfolobus tengchongensis spindle-shaped virus 1 (STSV1) coat protein as a prospective bioscaffold for nanotechnological applications. Extremophiles, 18(4): 745–754.
- Song L, Wang H, Wang S, Zhang H, Cong H, Tien P#. (2014). Memory effect of reversibly thermoswitchable self-assembly-competent recombinant TMV coat protein with multi-binding moieties with potential applications in nanoparticle purification. Journal of Materials Science, 49(7): 2693–2704.
Other work
- Zhang J, Zheng X, Wang H, Jiang H, Dong H, Huang L#. (2020). Novel Sulfolobus fuselloviruses with extensive genomic variations. Journal of Virology, 94(4): e01624-19.
- Erdmann S*, Chen B*, Huang X, Deng L, Liu C, Shah SA, Le Moine Bauer S, Sobrino CL, Wang H, Wei Y, She Q, Garrett RA, Huang L#, Lin L#. (2014). A novel single-tailed fusiform Sulfolobus virus STSV2 infecting model Sulfolobus species. Extremophiles, 18(1): 51–60.
- Xiang X*, Huang X*, Wang H*, Huang L#. (2015). pTC plasmids from Sulfolobus species in the geothermal area of Tengchong, China: genomic conservation and naturally-occurring variations as a result of transposition by mobile genetic elements. Life, 5(1): 506–520.
- Wang H, Peng N, Shah SA, Huang L#, She Q#. (2015). Archaeal extrachromosomal genetic elements. Microbiology and Molecular Biology Reviews, 79(1): 117–152.
