Given the deadly global rampage that HIV has been on for the past few decades, you’re all probably familiar with the virus. But you may not be aware that there are two types of HIV—HIV-1 and HIV-2—with the former being significantly more prevalent worldwide. The most common type of HIV-1 is then further divided into distinct subtypes, some of which are associated with a more rapid progression to AIDS. If these different viruses meet in an infected person, for example if someone infected with one subtype is exposed to a different one, they can exchange bits of their genetic material to create a new virus.
One of these so called “circulating recombinant forms” is currently spreading through Cuba, and it’s unfortunately extremely aggressive. Individuals infected with this hybrid virus, which is a mix of three different HIV-1 subtypes, progress to AIDS more than three times faster than average. Now, scientists have scrutinized this particularly pathogenic strain, which has yielded insight into the traits that have bestowed it with this deadly efficiency. The findings have been published in EBioMedicine.
Before HIV can get inside our cells, it first needs to bind to receptors on the surface called CD4. While this is an essential first step, it’s insufficient to get the virus inside. This is where anchoring points, called coreceptors, come in, which HIV also has to latch onto to gain entry. There are two coreceptors, CCR5 and CXCR4, and around 90% of newly transmitted HIV uses the former.
CXCR4-using viruses emerge in around 50% of individuals, but this usually takes around five years from infection. These viruses are associated with a more pronounced depletion of immune cells, but whether this shift in coreceptor preference is a cause or consequence of disease progression is unknown. Interestingly, however, the aggressive recombinant currently spreading through Cuba starts to use CXCR4 very early on in infection, and researchers think this is likely contributing to the observed rapid progression to AIDS.
To find this out, researchers examined 73 recently infected patients in Cuba, 52 who had rapidly progressed to AIDS within three years and 21 without AIDS. Then, they compared the blood of these individuals with 22 patients who had progressed to AIDS after the period typically expected, which is around 10-15 years without treatment.
They found that all those who had progressed to AIDS within three years of infection were infected with a recombinant called CRF19, which is a mixture of subtypes A, D and G. Interestingly, infection with A/D recombinants has previously been reported to result in rapid progression to AIDS, but no CRFs had been exclusively associated with rapid progression. Furthermore, those infected with CRF19 had abnormally high levels of an immune response molecule called RANTES, which acts by binding to CCR5. Without this coreceptor available for binding, CRF19 may have been forced to bypass that anchor point and go straight for CXCR4. Since the switch to CXCR4 usage is associated with progression to AIDS, this could explain why those infected with CRF19 developed AIDS so early on.
Another reason that CRF19 might be so pathogenic is that it has an enzyme, called protease, from subtype D, which is known to be very efficient. This enzyme helps the virus form mature particles, which is an essential stage in the virus life cycle.
[Via KU Leuven and EBioMedicine]