Type I interferons (IFN) are signaling molecules that trigger an antiviral response of innate and acquired immunity. There are numerous subtypes of IFN–alpha and IFN-beta among type I interferons. Although IFN-alpha and IFN-beta bind to the same receptor, their biological effects differ.
German scientists have investigated the effect of interferon-alpha-11 and beta on retroviruses that cause immunodeficiency and cancer. Retroviruses include the human immunodeficiency virus (HIV), which causes AIDS. Scientists studied mice infected with the Friend retrovirus, which causes leukemia.
Scientists have found that both IFN-alpha-11 and IFN-beta exhibit antiviral activity during acute retroviral infection. However, only interferon-alpha-11 suppresses chronic retroviral infection.
Type I Interferons are Used to Treat Hepatitis C And HIV
IFN-alpha-2 has been used in clinical practice since 1983. Unlike most antiviral drugs, IFN-alpha prevents infection of cells and suppresses the virus in cells. For a long time, IFN-alpha-2 has been effectively used to treat the hepatitis C virus, alone or in combination with other antiviral drugs. In 2016, scientists developed more effective direct-acting antiviral drugs to treat hepatitis C. Since then, IFN-alpha has no longer been used in hepatitis therapy. The cause was also the side effects of IFN-alpha-2, due to which 15% of patients stopped treatment.
In several clinical trials, IFN-alpha-2 was used as monotherapy or in combination with antiretroviral therapy for the treatment of HIV but did not show a clinical result. Recently, German scientists have investigated another subtype of interferon-alpha – IFN-alpha-14 – for the treatment of HIV. IFN-alpha-14, compared to IFN-alpha-2, suppressed HIV replication much more effectively. In addition, combination therapy with antiretroviral drugs together with IFN-alpha-14 reduced viral load in mice with chronic HIV infection.
Interferon-Beta Contributes to Chronic Retroviral Infection Instead of Alpha
Although interferons have an antiviral effect, they can be harmful in chronic viral infections. During chronic viral infections, type I interferon often causes hyperactivation of the immune system and destruction of lymphoid tissue, increasing the severity of the disease.
Several studies have shown that in mice with chronic HIV infection, IFN-I was associated with T-cell dysfunction and lack of immune control over the virus. However, scientists did not distinguish between interferon-beta and interferon-alpha responses in these studies.
American scientists recently investigated the chronic lymphocytic choriomeningitis virus and showed that only IFN-beta, not IFN-alpha, suppresses antiviral immunity and supports chronic infection. Thus, IFN-alpha can still be a treatment option for chronic disorders, including HIV.
German scientists have shown that with chronic infection of the Friend retrovirus, mice do not develop hyperactivation of the immune system, but T-killers are depleted. Treatment with IFN-alpha-11 triggers the expression of antiviral interferon-stimulated genes (ISG), suppresses virus replication and stimulates depleted T-killers that restore cytotoxic functions.
Conclusions
During acute retroviral infections, type I interferons inhibit virus replication. However, in chronic retroviral infections, IFN-I has the opposite effect. IFN-beta promotes immune dysfunction in chronic retroviral infections, but IFN-alpha-11 suppresses the virus and restores depleted T-killers. Interferon-alpha-11 may be beneficial for the treatment of HIV.
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