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

1
Cell and Gene Technology Group, Institute of Gene Biology RAS, 34/5 Vavilova Street, 119334 Moscow, Russia
2
Faculty of Biology, Lomonosov Moscow State University, 1-12 Leninskie Gory, 119991 Moscow, Russia
3
NRC Institute of Immunology FMBA of Russia, 24 Kashirskoe Shosse, 115472 Moscow, Russia
*
Author to whom correspondence should be addressed.
Viruses 2019, 11(5), 390; https://doi.org/10.3390/v11050390
Received: 22 February 2019 / Revised: 24 April 2019 / Accepted: 25 April 2019 / Published: 26 April 2019
(This article belongs to the Section Animal Viruses)
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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. View Full-Text
Keywords: HIV-1; accessory proteins; restriction factors; cell-to-cell infection; BST2; Vpu; Nef; CRISPR-Cas9 knockout HIV-1; accessory proteins; restriction factors; cell-to-cell infection; BST2; Vpu; Nef; CRISPR-Cas9 knockout
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Zotova, A.; Atemasova, A.; Pichugin, A.; Filatov, A.; Mazurov, D. Distinct Requirements for HIV-1 Accessory Proteins during Cell Coculture and Cell-Free Infection. Viruses 2019, 11, 390.

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