Fig. 4.

Scenarios of infection of B. natans cells by NCLDVs and virophages. Scenario (S)1 starts with B. natans cells devoid of VLE insertions. An NCLDV particle (yellow hexagon) or its DNA enters the cell and establishes viral factories (VFs) that produce new NCLDV particles. The infection causes cell lysis and death accompanied by release of NCLDV particles. Scenario 2 begins with B. natans cells carrying VLEs in the form of functional provirophages integrated in the nuclear genome (N). VLEs may have been produced by independent entry of a virophage followed by active DNA integration in the host nuclear genome (delayed-entry mode). Upon NCLDV infection, expressed VLE proteins may inhibit virus penetration or trigger reactivation and excision of the provirophage, which in turn inhibits NCLDV replication and takes advantage of the viral factories for its own replication. As a result, a limited number of NCLDV particles are created compared with S1, leading to increased rates of cell survival. Potentially, new virophages and a limited number of NCLDV particles are released in the environment through exocytosis or another unknown mechanism that does not kill the host cell.