Immune destruction of virus-infected cells early in the infectious cycle

Abstract

TARGET cells acutely infected with herpes simplex virus (HSV) can be destroyed by human blood mononuclear cells (MC) in the presence of IgG antibody to HSV^1–3, a process termed antibody-dependent cellular cytotoxicity (ADCC). The major effector cell which mediates this reaction is a K cell; it possesses surface Fc receptors which permit attachment to IgG antibody-sensitised target cells^4–6, although the way in which the lethal hit is delivered is poorly understood. For an immune cytolytic mechanism to be maximally effective in limiting the spread of virus in a host, it should be able to destroy the infected cell at an early stage in the viral maturation cycle, before infectious viral progeny can be produced. This requirement seems to be of particular importance for viruses such as HSV, which can avoid exposure to the neutralising antibody in extracellular fluid by spreading from cell to cell across intercellular bridges^7,8. In this report, we demonstrate that the ADCC mechanism can recognise viral surface antigens as early as 2 h after cells are infected with HSV and can produce target cell death by 3 h after infection (PI), well in advance of the first appearance of both viral progeny and the susceptibility of infected cells to lysis by antibody and complement (AbC).