Date Published: February 12, 2018
Publisher: Public Library of Science
Author(s): Adrienne L. McNees, Lindsay J. Harrigal, Aoife Kelly, Charles G. Minard, Connie Wong, Janet S. Butel, Michael Nevels.
Polyomaviruses, including simian virus 40 (SV40), display evidence of lymphotropic properties. This study analyzed the nature of SV40–human lymphocyte interactions in established cell lines and in primary lymphocytes. The effects of viral microRNA and the structure of the viral regulatory region on SV40 persistence were examined.
SV40 DNA was maintained in infected B cell and myeloid cell lines during cell growth for at least 28 days. Limiting dilution analysis showed that low amounts of SV40 DNA (~2 copies per cell) were retained over time. Infected B cells remained viable and able to proliferate. Genome copies of the SV40 microRNA-null mutant persisted at higher levels than the DNA of wild-type viruses. Complex viral regulatory regions produced modestly higher DNA levels than simple regulatory regions. Viral large T-antigen protein was detected at low frequency and at low levels in infected B cells. Following infection of primary lymphocytes, SV40 DNA was detected in CD19+ B cells and CD14+ monocytes, but not in CD3+ T cells. Rescue attempts using either lysates of SV40-infected B lymphocytes, coculture of live cells, or infectious center assays all showed that replication-competent SV40 could be recovered on rare occasions. SV40 infections altered the expression of several B cell surface markers, with more pronounced changes following infections with the microRNA-null mutant.
These findings indicate that SV40 can establish persistent infections in human B lymphocytes. The cells retain low copy numbers of viral DNA; the infections are nonproductive and noncytolytic but can occasionally produce infectious virus. SV40 microRNA negatively regulates the degree of viral effects on B cells.
Lymphocytes may serve as viral reservoirs and may function to disseminate polyomaviruses to different tissues in a host. To our knowledge, this report is the first extensive analysis of viral microRNA effects on SV40 infection of human lymphocytes.
The polyomavirus family is rapidly expanding [1,2]. However, the pathogenesis of infections by polyomaviruses in susceptible hosts and how those infections may lead to disease (usually in the immunocompromised) are not well-understood. Polyomaviruses are known to establish persistent infections in hosts, but the breadth of target tissues and the status of virus in those tissues remain obscure . Insights into the nature of viral infection and persistence in different cell types are needed.
This study addressed the nature of the interaction of polyomavirus SV40 with human lymphocytes. We found that B cells and myeloid cells can be infected by SV40. Viral genomes were maintained in established B cell lines (DG75, BJAB, RL) and a myeloid cell line (TF-1a) during several weeks of subculture following infection (Figs 1 and 6). In contrast, the amount of viral DNA retained in an infected T cell line (CEM) steadily decreased, paralleling the calculated loss of input virus by dilutions during cell passage (Fig 1).