The hypothesis explains 20 years of perplexing observations and suggests new ways to reduce HIV transmission and treat HIV infection, but it also implies that existing approaches to developing vaccines against HIV won't work. A description of the hypothesis and its supporting evidence appear in the Proceedings of the National Academy of Sciences, scheduled for publication online this week.
"Most researchers have focused on viral proteins when trying to understand HIV's mechanisms or develop vaccines," says James Hildreth, M.D., Ph.D., professor of pharmacology and molecular sciences in Hopkins' Institute for Basic Biomedical Sciences. "But so many aspects of retroviral biology have not been reconciled, including HIV, that we have to take a broader view. If our hypothesis is true and retroviruses can rely on human proteins, vaccines based solely on a few key viral proteins will never be able to completely prevent infection. There needs to be serious attention to this hypothesis."
Even if a vaccine against the viral proteins physically blocks a retrovirus's primary way of infecting cells, the retrovirus's ability to enter new cells by way of its cover of human proteins -- the Trojan horse -- provides previously unrecognized ways to escape the vaccine's effects, says Stephen Gould, Ph.D., professor of biological chemistry in the Institute for Basic Biomedical Sciences.
To go from cell to cell, all retroviruses are packaged in "envelopes" made from viral proteins and proteins from human cell membranes. The prevailing view is that the viral proteins do all the work to enter new cells, and the human proteins are just along for the ride. But the Hopkins team suggests that sometimes the viral proteins take the back seat, and the retrovirus r
Contact: Joanna Downer
Johns Hopkins Medical Institutions