Terry, A., Kilbey, A., Naseer, A., Levy, L. S., Ahmad, S., Watts, C., Mackay, N., Cameron, E. , Wilson, S. and Neil, J. C. (2017) Barriers to infection of human cells by feline leukemia virus: insights into resistance to zoonosis. Journal of Virology, 91(5), e02119-16. (doi: 10.1128/JVI.02119-16) (PMID:28031367) (PMCID:PMC5309941)
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Abstract
The human genome displays a rich fossil record of past gamma-retrovirus infections, yet no current epidemic is evident, despite environmental exposure to viruses that infect human cells in vitro. Feline leukemia viruses (FeLVs) rank high on this list, but domestic or workplace exposure has not been associated with detectable serological responses. Non-specific inactivation of gamma-retroviruses by serum factors appears insufficient to explain these observations. To investigate further we explored the susceptibility of primary and established human cell lines to FeLV-B, the most likely zoonotic variant. Fully permissive infection was common in cancer-derived cell lines, but was also a feature of non-transformed keratinocytes and lung fibroblasts. Cells of haematopoietic origin were less generally permissive and formed discrete groups on the basis of high or low intracellular protein expression and virion release. Potent repression was observed in primary human blood mononuclear cells and a subset of leukemia cell lines. However, the early steps of reverse transcription and integration appear to be unimpaired in non-permissive cells. FeLV-B was subject to G->A hypermutation with a predominant APOBEC3G signature in partially permissive cells but was not mutated in permissive cells or in non-permissive cells that block secondary viral spread. Distinct cellular barriers that protect primary human blood cells are likely to be important in protection against zoonotic infection with FeLV.
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