Virus-Induced Subversion of CTL Responses

Abstract

So far, this book has discussed how CTL responses can fight viral infections, leading to their successful resolution and clearance. On the other hand, viruses have the ability to avoid clearance by a variety of mechanisms. A very prominent mechanism that has been documented in the context of several pathogens is antigenic escape. Viral epitopes acquire mutations that prevent the CTL response from recognizing the epitope. Consequently, the infected cell is not attacked by the CTL. HIV is probably the best known virus that shows extensive antigenic escape [(1996); (1997); (2001); (1991); (1997a); (1999)]. Because HIV has a relatively high mutation rate, escape mutants are readily generated and this can contribute to the inability of the CTL response to fight HIV effectively, and it might contribute to the eventual development of AIDS. HCV infection is another example of a human pathogen that can readily acquire mutations, allowing it to escape from immune responses [(2000)]. Another mechanism to avoid immune-mediated clearance is to establish a latent infection [(1999)]. This means that cells can be infected by the virus, but once inside the cell, the virus is silent and does not produce further progeny viruses for prolonged periods of time. If the virus is silent, the CTL cannot recognize that the cell is infected, because no viral proteins are produced. If the cell is sufficiently long-lived, it can carry the virus and provide a reservoir for viral persistence. At certain time intervals, the virus can reactivate in the cells and start producing new virus particles. This is called the lytic phase of the infection, and the CTL response tends to prevent growth of the virus to high numbers. Thus, while the CTL manage to control the virus in this case, latent infection of cells prevents clearance of the virus.