Prevention of Apoptosis by a Baculovirus Gene During Infection of Insect Cells

Abstract

Programmed cell death is an active process of self destruction that is important in both the development and maintenance of multicellular animals. The molecular mechanisms controlling activation or suppression of programmed cell death are largely unknown. Apoptosis, a morphologically and biochemically defined type of programmed cell death commonly seen in vertebrates, was found to be initiated during baculovirus replication in insect cells. A specific viral gene product, p35, was identified as being responsible for blocking the apoptotic response. Identification of the function of this gene will allow further definition of the molecular pathways involved in the regulation of programmed cell death and may identify the role of apoptosis in invertebrate viral defense systems.

Modified vaccinia virus Ankara protein F1L is a novel BH3-domain-binding protein and acts together with the early viral protein E3L to block virus-associated apoptosis

“…An early and clear example of this situation was the demonstration that a baculovirus has the capacity to induce apoptosis in infected insect cells and that, at the same time, this capacity is countered by the expression of the viral gene p35. 4 Since then, apoptosis inhibitors have been found in viruses that infect diverse species, such as Epstein Barr virus, 5 African swine fever virus 6 and various baculoviruses. 7 In most of these cases, viral inhibitors of apoptosis are known cellular homologues, such as the antiapoptotic protein Bcl-2.…”

Caspase inhibitors: viral, cellular and chemical

“…P35, 34 and the related p49 from Spodoptera littoralis nucleopolyhedrovirus 35 inhibit a broad range of caspases. 14,17,36-38 P35 not only inhibits insect caspases, but also inhibits many mammalian caspases, mostly with Kds in the low nanomolar range 14 (Table 1).…”

Alternate functions of viral regulators of cell death

“…Although the 'lytic' (productive) replication cycles of many viruses indeed result in cell death, these viruses also trigger cells to commit suicide by activating a pathway of programmed cell death. [1][2][3][4] In multicellular organisms, and in colonies of single-cell species, the activation of cell suicide in response to a virus infection is thought to have arisen during evolution as an effective early defense strategy to prevent the spread of infection. 5,6 This ancient altruistic suicide mechanism of infected cells is a crucial component of the innate host response.…”

“…Mutant viruses lacking these genes have severe impairment of progeny virus production owing to premature death of host cells. 1,2,17,18 In addition to E1B-19K, E1B-55K and P35, many other types of antiapoptotic genes are encoded in viral genomes. Programmed death is viewed as the mechanism of choice to rid the host of virusinfected cells, as failure to do so often results in virus persistence, although noncytolytic mechanisms for clearing intracellular virus also exist.…”