On World AIDS Day, December 1, Scripps, Jupiter campus, researcher Susana Valente, Ph.D., delivered the first presentation in this season’s Front Line of Hope series.
Valente, assistant professor in the Department of Infectology at Scripps, has just been awarded a $3.4 million grant from the National Institutes of Health for HIV / AIDS research.
The first recognized cases were 30 years ago, when young men in New York City and Los Angeles, California began developing rare infections and cancers, she said, and at the time, no one knew what this was all about.
It became obvious that these men were suffering from the same syndrome, and by mid-1980s, Luc Montagnier of the Pasteur Institute and Robert Gallo of the National Cancer Institute identified the viral agent and gave it a name, Human Immunodeficiency Virus.
By 1998, scientists who were analyzed older plasma samples from the 1950s, with features of HIV, and thought that HIV had been introduced to the United States in the 1940s and 1950s.
HIV is a part of a group of “slow” viruses, also part of a bigger group, called retroviruses, common in many species. SIV, or Simian Immunodeficiency Virus, is a retrovirus that’s found in apes, and has been around for at least 32,000 years.
HIV-1 and HIV-2, crossed the species barrier to humans. HIV-1 evolved from SIV from a subspecies of chimpanzees and HIV-2 evolved from SIV from white-collared monkeys.
How did that happen? Most likely, while butchering and consuming ape meat, the ape blood got into cuts or wounds of African hunters, Valente explained.
In the 30 years, HIV spread quickly. By 2007, 33-million people are living with HIV/AIDS and 25 million have died. 1.2 million people have HIV/AIDS in the United States, and the third highest concentration of infected people is here in South Florida, right behind New York and California.
For incidences of new infections, (2006 numbers) five of the top 15 cities are in South Florida.
There are 121,000 people with HIV/AIDS in Florida. Last year, 5,200 new cases reported of HIV infection, and 4,400 cases with AIDS and 1,600 have passed away from the disease.
In Florida, half of the HIV population is Black, and that’s a big number, considering that only 14 percent of Florida’s population is Black.
And the group of infected people over 50 years old is a growing number, 27 percent of the total number. Of that group ¾ are male. “That percentage holds true in the United States, and those who died in 2010, 50 percent were more than 50 years old.
HAART (Highly Active Antiretroviral Therapy) was introduced in 1996, and formalized by the FDA in 2001. This therapy targets at least two steps of the life-cycle of the virus.
The problem with HAART is that patients become resistant to the treatment. And because it has side effects (nausea / liver damage), patients fail to take their medication consistently, which is essential for the regimen to work.
And, there are no vaccines, because HIV evolves quickly, making it impossible for an antibody to fight the disease.
Other problems: There are many combinations of the virus, making it hard to be treated by a vaccine. Also, the virus can hide from the immune system, and, finally, for studies and research, there is no animal model that is appropriate.
So, “we need new viruses that target different aspects of viral replication and better safety profiles. There’s lots left to be done,” she said. “A popular approach is to try to find compounds that block the proteins in the cell that the virus needs to replicate. It’s easier if we can target the proteins that the virus uses rather than trying to target the virus itself.”
Here, Valente gave a basic lesson on cells, cell transcription, post-translational modifications, and how and where the virus takes advantage of the cells and those processes.
There are different stages where the virus can be stopped within the cell, and her team is looking for proteins that will do just that.
“We know that certain cells can be infected by the HIV virus, but some cells cannot be infected and those resistant cells can be made or we can make them resistant. A third way, we can give them some signaling molecules that put them in an antiviral state (that’s what happens when we fight any infection). We want to know about the anti-resistant state.
“So, we take the cells that are resistant and see what DNA is making it resistant.
“We have found two cell lines that are very resistant: H1 and H2.”
H1 blocks the RNA of the virus from coming out of the nucleus of the cell into the cytoplasm (so the later viral steps are abolished), and H2 stops the RNA from becoming mRNA.
“We also need to devise chemicals to mimic what those proteins are doing.”
In addition, a new compound that blocks TAT has been discovered.
One of the first proteins produced by the virus is TAT, which pairs up with viral DNA in the nucleus. “It’s like gas for a car. If we can stop TAT from acting, we can control replication of the virus.”
A compound, SV101 (isolated from marine sponges) does the job.
“If we take infected cells and treat them with SV101, we drastically drop the RNA that is expressed. It also changes where TAT is in the cell, excluding it from the nucleus, which is associated with lack of activity.
Front Line of Hope is an educational invitation-only series. To request an invitation or further information on the 2011-2012 Front Lines of Hope program, call (561) 228-2084 or email Philanthropy-Florida@scripps.edu.
copr. 2011 Christine Davis