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Cited by 11HIV Research and TreatmentT-cell and Retrovirus StudiesVirus-based gene therapy research

Distinct Requirements for HIV-1 Accessory Proteins during Cell Coculture and Cell-Free Infection

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Zotova, Anastasia, Atemasova, Anastasia, Pichugin, Alexey, Filatov, Alexander, Mazurov, Dmitriy·2019·Viruses
DOI 10.3390/v11050390PMC PMC6563509
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Abstract

The role of accessory proteins during cell-to-cell transmission of HIV-1 has not been explicitly defined. In part, this is related to difficulties in measuring virus replication in cell cocultures with high accuracy, as cells coexist at different stages of infection and separation of effector cells from target cells is complicated. In this study, we used replication-dependent reporter vectors to determine requirements for Vif, Vpu, Vpr, or Nef during one cycle of HIV-1 cell coculture and cell-free infection in lymphoid and nonlymphoid cells. Comparative analysis of HIV-1 replication in two cell systems showed that, irrespective of transmission way, accessory proteins were generally less required for virus replication in 293T/CD4/X4 cells than in Jurkat-to-Raji/CD4 cell cocultures. This is consistent with a well-established fact that lymphoid cells express a broad spectrum of restriction factors, while nonlymphoid cells are rather limited in this regard. Remarkably, Vpu deletion reduced the level of cell-free infection, but enhanced the level of cell coculture infection and increased the fraction of multiply infected cells. Nef deficiency did not influence or moderately reduced HIV-1 infection in nonlymphoid and lymphoid cell cocultures, respectively, but strongly affected cell-free infection. Knockout of BST2—a Vpu antagonizing restriction factor—in Jurkat producer cells abolished the enhanced replication of HIV-1 ΔVpu in cell coculture and prevented the formation of viral clusters on cell surface. Thus, BST2-tethered viral particles mediated cell coculture infection more efficiently and at a higher level of multiplicity than diffusely distributed virions. In conclusion, our results demonstrate that the mode of transmission may determine the degree of accessory protein requirements during HIV-1 infection.

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  • Cell-to-cell infection enhances co-transmission of two different strains of HIV-1 in vitro and in vivo; cell-cell contact can increase multiplicity of infection and diversity of HIV.

    “Law et al. have shown that cell-to-cell infection enhances co-transmission of two different strains of HIV-1 in vitro and in vivo [129]. This is well consistent with our results obtained using cell lines and two reporter vectors, inGFPt and in-mCherry [131], suggesting that cell-cell contact can increase multiplicity of infection and diversity of HIV.”

    From HIV-1 and HTLV-1 Transmission Modes: Mechanisms and Importance for Virus Spread (2022) · cites this paper as [131]

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Authors
Zotova, A., Atemasova, A., Pichugin, A., Filatov, A., & Mazurov, D.
Affiliations
  • Russian Academy of Sciences (RU)
  • Lomonosov Moscow State University (RU)
  • NRC Institute of Immunology FMBA of Russia, 24 Kashirskoe Shosse, 115472 Moscow, Russia
  • Federal Medical-Biological Agency (RU)
  • Institute of Gene Biology (RU)
Corresponding author
Mazurov, Dmitriy
ORCID
Venue
Viruses
Publisher
MDPI AG
Published
2019-04-26
Volume
11
Issue
5
Pages
390
ISSN
1999-4915 (ISSN-L)
DOI
10.3390/v11050390
PMC
PMC6563509
OpenAlex
W2941938899
Cited by
11
References
1
Citations by year
2025: 2 · 2023: 3 · 2022: 3 · 2021: 1 · 2020: 1 · 2019: 1
FWCI
0.84
Type
journal article
Language
en
Open access
Licence
Locations
  • Viruses (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Russian Science Foundation (15-15-00135, 18-14-00333)
Topics
  • Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and Retrovirus Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
Keywords
HIV-1 accessory proteins, Vpu, Vif, Vpr, NEF, cell-to-cell transmission, BST2, host restriction factors, viral replication, lymphoid cells, Jurkat cells
MeSH terms
Viroporin Proteins, Cell Line, Cell-Free System, Cells, Cultured, Humans, Mutation, Virus Replication, CD4-Positive T-Lymphocytes, HIV-1, HIV Infections, Gene Expression Regulation, Viral, Coculture Techniques, Jurkat Cells, Human Immunodeficiency Virus Proteins, nef Gene Products, Human Immunodeficiency Virus, Viral Regulatory and Accessory Proteins, Gene Knockdown Techniques

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