Soon after identification of HIV as the cause of AIDS, several researchers treated infected patients with alpha-interferon, a naturally occurring “type Ⅰ” interferon. This seemed to be a logical intervention, given the ability of such interferons to inhibit many viruses, including HIV, in the test tube and their potential to suppress the growth of Kaposi sarcoma, a common form of AIDS-related cancer.
But interferon therapy had little effect on HIV-infected patients and was soon abandoned in favor of potent antiretroviral therapies (ART).
In an editorial in the January issue of The Journal of Clinical Investigation, amfAR-funded scientist Dr. Steven Deeks of the University of California, San Francisco (UCSF), working with colleagues from UCSF and Case Western Reserve University in Cleveland, Ohio, outline another approach involving interferon that may be superior at achieving HIV suppression.
Deeks and associates discuss two recent studies involving BLT mice, immunodeficient animals with a human immune system formed from injections of human bone marrow, liver, and thymus cells. These mice can be infected with HIV and treated with ART.
From these studies and earlier experiments, it appears that interferon is a double-edged sword in combating HIV disease, according to the researchers. In the initial phase of infection, it can suppress growth of HIV.
In one experiment, antibodies were administered to block interferon in monkeys infected with SIV, the monkey (simian) form of HIV. The monkeys were unable to control the virus and died rapidly.
But in the mouse models, if interferon was blocked in the chronic phase, while the mice were receiving ART, there was a decrease in HIV growth and a reduction in latently infected cells.
The researchers conclude that interferon is harmful during chronic infection as it “reshapes” the immune response, promoting viral replication and inflammation. They note that using antibodies in the chronic phase to block type I interferon, as in the two mouse models, improved viral control by three mechanisms: suppressing T cell activation, thus reducing the pool of T cells that are producing virus or susceptible to new infection; decreasing HIV-infected CD4+ T cell proliferation; and increasing CD8+ killer T cell function.
In a twist on the concept of “shock and kill,” in which drugs are used to push the virus out of latently infected cells, Deeks and colleagues suggest that the increased killer T cell function resulting from interferon suppression late in infection, in concert with temporary “blips” of viral growth associated with blocking interferon early in infection, would be a novel means of controlling the HIV reservoir.
And thus bring us a step closer to an HIV cure.
Dr. Laurence is amfAR’s senior scientific consultant.