Human natural killer cells limit replication of herpes simplex virus type 1 in vitro Journal Article
| Authors: | Fitzgerald, P. A.; Mendelsohn, M.; Lopez, C. |
| Article Title: | Human natural killer cells limit replication of herpes simplex virus type 1 in vitro |
| Abstract: | Studies were undertaken to determine whether natural killer (NK) cells could inhibit the replication of herpes simplex virus type 1 (HSV-1) in culture. In the absence of effector cells, HSV-1 was found to replicate in fibroblasts with up to a 100-fold increase in virus titer from 4 to 16 hr after incubation at 37°C. Human peripheral blood mononuclear cells were found to limit virus replication in a dose-dependent manner, with the greatest inhibition being observed at the highest concentration evaluated: i.e., an effector:target ratio of 800:1. The antivirial effect was not observed when nonactivated or virus-activated mononuclear cells were added to the virus preparations at the end (instead of the beginning) of the assay period, indicating that the observed effect was not due to a nonspecific toxicity of soluble factors released from freeze-thawed effectors. Neither was inhibition of HSV-1 replication due to the generation of interferon (IFN) during the NK assay, because the addition of anti-IFN did not abrogate the antiviral effect. Thus, the inhibition of viral replication was most likely due to a cytotoxic effector rather than to release of soluble factors. The effector cells responsible for limiting HSV-1 replication were shown to be NK cells by a number of criteria. 1) Mononuclear cells from both HSV-1 seropositive and seronegative donors limited virus replication; 2) their activity could be boosted by pretreatment of effector cells with IFN; 3) the effector cells which limited virus replication were found in Percoll gradient fractions enriched for large granular lymphocytes; and 4) the effector cells shared the cell surface phenotype of NK cells - they were enriched in populations depleted to T cells by panning with Leu-4 and were depelted of activity by treatment with the anti-NK antibody Leu-11b plus complement. We conclude that human NK cells are capable of recognizing and lysing HSV-1-infected target cells before infectious virus progeny are generated. These results suggest that NK cells, acting early in the course of an infection, might serve to limit HSV-1 replication and therefore reduce the virus load in the host before the development of the adaptive immune response and clearance of the infection. |
| Keywords: | interferon; in vitro study; blood; cell culture; natural killer cell; radioisotope; virus replication; herpes simplex virus 1; human; priority journal; blood and hemopoietic system |
| Journal Title: | Journal of Immunology |
| Volume: | 134 |
| Issue: | 4 |
| ISSN: | 0022-1767 |
| Publisher: | The American Association of Immunologists, Inc |
| Date Published: | 1985-04-01 |
| Start Page: | 2665 |
| End Page: | 2672 |
| Language: | English |
| PROVIDER: | scopus |
| PUBMED: | 2982949 |
| DOI: | 10.4049/jimmunol.134.4.2666 |
| DOI/URL: | |
| Notes: | Export Date: 26 October 2021 -- Source: Scopus |
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