The viruses hepatitis B (HBV, a DNA virus) and hepatitis C (HCV, an RNA virus) infect the liver and cause acute and chronic hepatitis, liver cirrhosis, and in some cases hepatocellular carcinoma. Immune responses probably have an important role in the clearance of both types of hepatitis infection, but in many cases HBV and HCV set up a chronic infection. Although HCV mainly infects the liver during the early stage of a primary infection, the virus subverts the adaptive immune response by interfering with dendriticcell activation and maturation. This leads to inadequate activation of CD4 T cells and a consequent lack of TH1 cell differentiation, which is thought to be responsible for the infection becoming chronic, most probably because of the lack of CD4 Tcell help to activate naive CD8 cytotoxic T cells. There is evidence that the decrease in levels of viral antigen seen after antiviral treatment improves CD4 Tcell help and allows the restoration of cytotoxic CD8 Tcell function and memory CD8 Tcell function. The delay in dendriticcell maturation caused by HCV is thought to synergize with another property of the virus that helps it to evade an immune response: the RNA polymerase that the virus uses to replicate its genome lacks proofreading capacity. This contributes to a high viral mutation rate and thus a change in its antigenicity, which allows it to evade adaptive immunity.
Summary.
Infectious agents can cause recurrent or persistent disease by avoiding normal host defense mechanisms or by subverting them to promote their own replication. There are many different ways of evading or subverting the immune response. Antigenic variation, latency, resistance to immune effector mechanisms, and suppression of the immune response all contribute to persistent and medically important infections. In some cases the immune response is part of the problem: some pathogens use immune activation to spread infection, and others would not cause disease if it were not for the immune response. Each of these mechanisms teaches us something about the nature of the immune response and its weaknesses, and each requires a different medical approach to prevent or to treat infection.
Acquired immune deficiency syndrome.
The most extreme example of immune subversion by a pathogen is the acquired immune deficiency syndrome (AIDS) caused by the human immunodeficiency virus (HIV). The disease is characterized by a progressive loss of CD4 T cells, which, when they have become sufficiently depleted, results in high susceptibility to opportunistic infections and certain malignancies. The earliest documented case of HIV infection in humans to date was reported in a sample of serum from Kinshasa (Democratic Republic of the Congo) that was stored in 1959. It was not until 1981, however, that the first cases of AIDS were officially reported. Because the disease seemed to be spread by contact with body fluids, the cause was suspected to be a new virus, and by 1983 the causative agent, HIV, was isolated and identified.
There are at least two types of HIV—HIV1 and HIV2—that are closely related. While both types are transmitted by sexual contact and bloodborne exposure (for example, blood transfusion, shared needles), HIV1 replicates to higher viral loads in blood and is therefore more easily transmitted; HIV1 has a high rate of transmission from mother to child, which is uncommon in HIV2. Although disease is indistinguishable in patients who progress to AIDS, HIV1 progresses to AIDS more rapidly and with greater incidence than HIV2. HIV1 is therefore by far the most prevalent cause of AIDS worldwide. And while both HIV1 and HIV2 are endemic to West Africa, HIV2 is rarely found elsewhere.
Both viruses seem to have originally spread to humans from other primate species in Africa. Viral genome sequencing of isolates suggests that the primate precursor of HIV1, simian immunodeficiency virus (SIV), has passed