Science (New York, N.Y.) · 2024
Engineered deletions of HIV replicate conditionally to reduce disease in nonhuman primates.
СтатьяПоддержка исследования: вне правительства СШАПоддержка NIH: внешняя программаНазвание и аннотация: Перевод в очереди
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Pitchai Fathima N Nagoor, Tanner Elizabeth J, Khetan Neha, Vasen Gustavo, Levrel Clara, Kumar Arjun J, Pandey Shilpi, Ordonez Tracy, Barnette Philip, Spencer David, Jung Seung-Yong, Glazier Joshua, Thompson Cassandra, Harvey-Vera Alicia, Son Hye-In, Son Hye-In, Strathdee Steffanie A, Holguin Leo, Urak Ryan, Burnett John, Burgess William, Busman-Sahay Kathleen, Estes Jacob D, Hessell Ann, Fennessey Christine M, Keele Brandon F, Haigwood Nancy L, Weinberger Leor S
Аннотация
Antiviral therapies with reduced frequencies of administration and high barriers to resistance remain a major goal. For HIV, theories have proposed that viral-deletion variants, which conditionally replicate with a basic reproductive ratio [R0] > 1 (termed "therapeutic interfering particles" or "TIPs"), could parasitize wild-type virus to constitute single-administration, escape-resistant antiviral therapies. We report the engineering of a TIP that, in rhesus macaques, reduces viremia of a highly pathogenic model of HIV by >3log10 following a single intravenous injection. Animal lifespan was significantly extended, TIPs conditionally replicated and were continually detected for >6 months, and sequencing data showed no evidence of viral escape. A single TIP injection also suppressed virus replication in humanized mice and cells from persons living with HIV. These data provide proof of concept for a potential new class of single-administration antiviral therapies.