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Comparison of a Genotype 1 and a Genotype 2 Macaque Foamy Virus <i>env</i> Gene Indicates Distinct Infectivity and Cell-Cell Fusion but Similar Tropism and Restriction of Cell Entry by Interferon-Induced Transmembrane Proteins
oleh: Thomas Fricke, Sarah Schlagowski, Shanchuan Liu, Xiaoliang Yang, Uwe Fiebig, Artur Kaul, Armin Ensser, Alexander S. Hahn
| Format: | Article |
|---|---|
| Diterbitkan: | MDPI AG 2023-01-01 |
Deskripsi
Foamy viruses (FVs) are naturally found in many different animals and also in primates with the notable exception of humans, but zoonotic infections are common. In several species, two different envelope (<i>env</i>) gene sequence clades or genotypes exist. We constructed a simian FV (SFV) clone containing a reporter gene cassette. In this background, we compared the <i>env</i> genes of the SFVmmu-DPZ9524 (genotype 1) and of the SFVmmu_R289hybAGM (genotype 2) isolates. SFVmmu_R289hybAGM <i>env</i>-driven infection was largely resistant to neutralization by SFVmmu-DPZ9524-neutralizing sera. While SFVmmu_R289hybAGM <i>env</i> consistently effected higher infectivity and cell-cell fusion, we found no differences in the cell tropism conferred by either <i>env</i> across a range of different cells. Infection by both viruses was weakly and non-significantly enhanced by simultaneous knockout of interferon-induced transmembrane proteins (IFITMs) 1, 2, and 3 in A549 cells, irrespective of prior interferon stimulation. Infection was modestly reduced by recombinant overexpression of IFITM3, suggesting that the SFV entry step might be weakly restricted by IFITM3 under some conditions. Overall, our results suggest that the different <i>env</i> gene clades in macaque foamy viruses induce genotype-specific neutralizing antibodies without exhibiting overt differences in cell tropism, but individual <i>env</i> genes may differ significantly with regard to fitness.