Controlling HIV infection by targeting seminal proteins
Human immunodeficiency virus (HIV) is commonly transmitted sexually through an HIV-infected partner. The virus can also be passed on via infected blood, semen or vaginal secretions, with semen being the primary vector. Semen contains amyloid fibrils, which help the virus to attach to the host cells, boosting HIV infectivity by 10,000 fold!
Researchers from the University of Pennsylvania suggested that, the most effective way to reduce/ stop HIV transmission could be by diminishing amyloid fibrils in semen. Two separate studies demonstrate this:
- The first study, published in the journal Chemistry & Biology in 2012, illustrated how Hsp104, a yeast heat-shock protein reacted with amyloid fibrils to convert them into non-amyloid forms. The team also developed an inactive variant of Hsp104 that disrupted the organization of amyloid fibrils, leading to harmless aggregated-protein structures. The modified Hsp104 along with an enzyme also degraded amyloid fibrils in semen.
- The second one, recently published in eLife, by a research team from the Ulm University Medical Center, Germany revealed how a small ‘tweezer shaped’ molecule, CLRO1 interfered the amyloid fibrils’ ability to enhance HIV transmission by destroying the pre-formed fibrils. CLRO1 has also been shown to interfere with HIV particles outer coat and dismantle particles already attached to amyloid fibrils leading to the reduction of the likelihood of HIV transmission by more than 100-fold. Astonishingly CLRO1 showed no affinity to other cell membranes, thereby suggesting the possible and safe incorporation of CLRO1 into vaginal or anal gel to prevent the infection.
Both the strategies diminished the ability of the amyloid fibrils’ to boost HIV transmission, showing potential therapeutic implication.
The ability of CLR01 to ‘block’ amyloid fibrils activity showed that it would also be effective against many other sexually transmitted viruses, like, Hepatitis C, human cytomegalovirus and viruses of herpes family and many other “enveloped” viruses like common flu and Ebola. But it was shown to be ineffective against the non-enveloped virus like, human adenovirus type 5.
The protein components of Amyloid fibrils in the brain are associated with neuro-degenerative disorders, such as Parkinson’s disease. As the action of CLRO1 is linked to amyloid fibres, CLRO1 could also offer Breakthrough Treatment for these Degenerative Diseases.
CLRO1 has been tested and found to be safe in zebrafish and mice. Next the team plans to assess its safety and efficacy in non-human primates.
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