Slow, progressive infection

A very few viruses persist within the infected host for extremely long periods of time before they develop an inevitable symptomatic infection. The most well-known virus giving rise to this type of slow, progressive infection is HIV. The virus initiates an acute, primary infection in T4 lymphocytes and other cells (macrophages, monocytes, and dendritic cells), leading to the development of anti-HIV antibodies and the transmission of virus in a range of body fluids. Following this primary infection and incomplete clearance, the virus can show a period of latency in infected T4 lymphocytes that reactivates as the cells are activated some time later.  If untreated, in most individuals the virus will eventually progress to more rapid replication and will ultimately cause the clinical syndrome known as acquired immune deficiency syndrome, AIDS. A small subset of individuals infected with HIV has not, after more than 20 years without antiviral treatment, shown progression of virus infection to AIDS. These individuals have a genetic mutation that results in a truncated CCR5 molecule on the surface of their macrophages. The incomplete CCR5 molecules do not function as normal co-receptors for HIV attachment, blocking pen- etration of the virus into cells and thereby preventing infection. This is an elegant and extremely important example of how molecular knowledge of a virus replication cycle can inform us about the progression and outcome of a serious disease, which may shed light on future treatments.

A less well-known example of a slow, progressive infection is that which develops in very rare cases of individuals infected by measles virus.  In the majority of cases measles is ashort-lived acute infection, but in a very small minority of cases (1 in 100 000) the virus is not completely cleared by the immune system, and establishes a low-level infection within the brain. The infection proceeds very slowly, and over time several mutations accumulate in the newly synthesized viral genomes. These mutations result in a failure to synthesize all the viral structural proteins, which means that the virus remains unde- tected by the immune system. Eventually (8–10 years later) infected cells die within the brain, leading to a disease known as subacute sclerosing panencephalitis (SSPE), which is untreatable and fatal.