Increased Susceptibility of Herpes simplex Virus-1 Growth in Phytohemagglutinin-Activated T Lymphocytes Caused by Upregulation of Herpesvirus Entry Mediator A mRNA Expression

Abstract

Objectives: To study herpes simplex virus (HSV) growth in human T lymphocytes (Jurkat cells) with and without phytohemagglutinin (PHA) activation and to investigate the possible mechanism of viral growth. Methods: The levels of HSV-1 production and adsorption were determined by plaque titration assay. The number of HSV-1-infected cells was assayed using flow cytometry. The expression of herpesvirus entry mediator A (HveA) mRNA was detected by RT-PCR. Results: HSV-1 production as well as the number of HSV-1-infected Jurkat cells were enhanced after the cells were activated by PHA. Moreover, the amount of viral entry was demonstrated to increase in PHA-activated cells. An increase in HveA mRNA was observed in PHA-activated Jurkat cells. Conclusions: We found that HSV-1 can replicate in human T lymphocytes, and the replication was increased following PHA activation. This finding may be due to an increase in viral entry via HveA receptor.

One of the Mechanisms to Increase HSV-1 Uptake in HSV-1-Infected, Activated T Lymphocytes Is the Formation of Filopodia

“…HVEM, a gD receptor, is expressed in wild-type cells, especially in immune cells. It has been previously shown that expression of HVEM is upregulated in PHA-activated Jurkat cells[10]. As a result, HVEM may be associated with the enhancement of HSV-1 entry into the host cell as well as promote the growth of the virus.…”

“…The tissue tropism of HSV infection is known to consist of epithelial cells and fibroblasts which are present in the mucocutaneous tissue and skin. However, HSV can also replicate in lymphocytes, suggesting that HSV can be transmitted to other people via blood [10]. Several studies have reported that HSV replication is poor in T lymphocytes, but excellent in mitogen-activated T lymphocytes.…”

“…The HVEM receptor has previously been reported to be upregulated in PHA-activated Jurkat cells 24 h after infection [10]. As a result, the authors investigated the expression of HVEM in anti-CD3-activated Jurkat cells.…”

“…Aside from E2F-1 and ICP4 proteins, another possible host-activated protein that may enhance HSV-1 production in activated T lymphocytes is the HSV receptor, e.g. the Herpes virus entry mediator (HVEM), a glycoprotein (g) D receptor [10]. When the T lymphocytes were activated with PHA, there was an increased expression of HVEM.…”

HIV-1 Replication in HIV-Infected Individuals Is Significantly Reduced When Peripheral Blood Mononuclear Cells Are Superinfected with HSV-1

“…In order for HSV to enter the cell, many host cell surface receptors are required. For example, herpes viral entry mediator (HVEM), a receptor that restricts expression of immune cells especially of lymphocytes [12, 13], increases when activated with mitogens such as phytohemagglutinin [14]. This activation increases HSV-1 production in the T lymphocytes [14].…”