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Peer-reviewedCC BY 4.0Microbiology and Immunology

Naturally Occurring ZCCHC3 Variants Modulate Antiretroviral Activity in Cynomolgus Macaques

  • Jacob Fadipe1,2
  • Tomotaka Okamura3,4
  • Shige H. Yoshimura5
  • Akatsuki Saito1,6,7,8
8 affiliations
  1. 1Laboratory for Viral Infection Control, Frontier Science Research Center University of Miyazaki Miyazaki Japan
  2. 2Department of Clinical and Biomedical Sciences, Faculty of Health and Life Sciences University of Exeter Exeter England
  3. 3Laboratory Animal and Pathogen Bank, Research Center for Biosafety, National Institute of Infectious Diseases Japan Institute for Health Security Tokyo Japan
  4. 4Tsukuba Primate Research Center, National Institutes of Biomedical Innovation Health and Nutrition Ibaraki Japan
  5. 5Faculty of Science Kyushu University Fukuoka Japan
  6. 6Department of Veterinary Science, Faculty of Agriculture University of Miyazaki Miyazaki Japan
  7. 7Graduate School of Medicine and Veterinary Medicine University of Miyazaki Miyazaki Japan
  8. 8Center for Animal Disease Control University of Miyazaki Miyazaki Japan
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Abstract

Many mammalian cells restrict viral replication by utilizing various host restriction factors. We recently demonstrated that CCHC‐type zinc‐finger‐containing protein 3 (ZCCHC3) suppresses human immunodeficiency virus type 1 (HIV‐1) replication through multiple mechanisms. We also revealed that single‐nucleotide polymorphisms in human ZCCHC3 affect its antiviral function; however, whether similar genetic and functional diversity is present in other species remains unknown. In this study, we investigated the genetic and functional diversity of ZCCHC3 in cynomolgus macaques, a critical animal model for HIV‐1‐related research. Sequencing analysis of eight independent ZCCHC3 clones per animal revealed substantial amino acid diversity among cynomolgus macaques. We selected 12 representative variants and examined their antiviral activity against several retroviral vectors derived from HIV‐1, simian immunodeficiency virus, feline immunodeficiency virus, and murine leukemia virus. Moreover, using replication‐competent HIV‐1, we showed that selected cynomolgus macaque ZCCHC3 variants can affect both viral production and viral infectivity. These results suggest that the genetic and functional diversity of ZCCHC3 is not limited to humans and underscore the importance of considering ZCCHC3 variation in cynomolgus macaques when using them as animal models for HIV‐1‐related research.

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Cite

BibTeXRIS
BibTeX
@article{fadipe2026naturally,
  title = {{Naturally Occurring ZCCHC3 Variants Modulate Antiretroviral Activity in Cynomolgus Macaques}},
  author = {Jacob Fadipe and Tomotaka Okamura and Shige H. Yoshimura and Akatsuki Saito},
  journal = {Microbiology and Immunology},
  year = {2026},
  month = sep,
  doi = {10.1111/1348-0421.70088},
  url = {https://doi.org/10.1111/1348-0421.70088},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Naturally Occurring ZCCHC3 Variants Modulate Antiretroviral Activity in Cynomolgus Macaques
AU  - Jacob Fadipe
AU  - Tomotaka Okamura
AU  - Shige H. Yoshimura
AU  - Akatsuki Saito
PY  - 2026
DA  - 2026/09/04
JO  - Microbiology and Immunology
DO  - 10.1111/1348-0421.70088
UR  - https://doi.org/10.1111/1348-0421.70088
AB  - Many mammalian cells restrict viral replication by utilizing various host restriction factors. We recently demonstrated that CCHC‐type zinc‐finger‐containing protein 3 (ZCCHC3) suppresses human immunodeficiency virus type 1 (HIV‐1) replication through multiple mechanisms. We also revealed that single‐nucleotide polymorphisms in human ZCCHC3 affect its antiviral function; however, whether similar genetic and functional diversity is present in other species remains unknown. In this study, we investigated the genetic and functional diversity of ZCCHC3 in cynomolgus macaques, a critical animal model for HIV‐1‐related research. Sequencing analysis of eight independent ZCCHC3 clones per animal revealed substantial amino acid diversity among cynomolgus macaques. We selected 12 representative variants and examined their antiviral activity against several retroviral vectors derived from HIV‐1, simian immunodeficiency virus, feline immunodeficiency virus, and murine leukemia virus. Moreover, using replication‐competent HIV‐1, we showed that selected cynomolgus macaque ZCCHC3 variants can affect both viral production and viral infectivity. These results suggest that the genetic and functional diversity of ZCCHC3 is not limited to humans and underscore the importance of considering ZCCHC3 variation in cynomolgus macaques when using them as animal models for HIV‐1‐related research.
SN  - 0385-5600
SN  - 1348-0421
ER  -