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Defective HIV-1 proviruses produce novel protein-coding RNA species in HIV-infected patients on combination antiretroviral therapy

2016; National Academy of Sciences; Volume: 113; Issue: 31 Linguagem: Inglês

10.1073/pnas.1609057113

1091-6490

Hiromi Imamichi, Robin Dewar, Joseph W. Adelsberger, Catherine Rehm, Una O’Doherty, Ellen E. Paxinos, Anthony S. Fauci, H. Clifford Lane,

Cytomegalovirus and herpesvirus research

Significance The presence of “defective” HIV-1 proviruses in HIV-infected patients has been well documented. The current consensus view of the “defective” proviruses is that these are dead-end products that do not give rise to progeny virus and thus collectively represent a “graveyard” of viruses. We describe the presence of defective HIV-1 proviruses capable of transcribing novel unspliced HIV-RNA species in HIV-infected patients on combination antiretroviral therapy. We propose that the proviruses persistently present in combination antiretroviral therapy-treated patients are not defective in a conventional sense, but rather represent incomplete forms of proviruses encoding translationally competent HIV-RNA transcripts. Strategies directed toward curing HIV-1 infection and eliminating the state of persistent immune activation need to include approaches designed to eliminate cells harboring such proviruses.