Jeannette Tenthorey
University of California-San Francisco, CA·Microbiology & Immunology·Early-career
HIV is hard to treat because it evolves so quickly: it can accumulate mutations that let it escape even combinations of drugs. The same flexibility lets it slip past the body's built-in antiviral defenses, proteins made inside our own cells that recognize incoming viruses before the immune system mounts a broader response.
- Fields
Microbiology & Immunology
Genetics
Biochemistry
- Topics
HIV-1 capsid
innate immunity
restriction factors
- Grants
- 1 known grant, through Jul 2029
What they work on
- Build stable, high-complexity HIV-1 libraries containing all possible single missense mutations across the capsid, using new tools that overcome long-standing barriers to producing saturating mutant viral libraries.
- Measure the fitness of every capsid variant during normal infection to define which positions and chemical changes are deleterious because the capsid must interact with host factors the virus requires.
- Test the same capsid mutation libraries in cells expressing human restriction factors TRIM5α, MxB, and TRIM34 — cell-intrinsic proteins that detect incoming capsids — to identify which mutations grant escape.
- Use the combined fitness maps to locate capsid positions where escape is evolutionarily constrained, identifying sites that drugs could target so escape sensitizes the virus to innate immunity.
More about the research
One of the virus's most exposed targets is the capsid, the protein shell that carries HIV's genetic material into a cell. Human capsid-sensing defense proteins barely slow HIV down, and it has not been clear which capsid changes are responsible, because sequencing viruses from patients shows which mutations exist but not which pressures selected them.
Why it matters
HIV's ability to evolve around therapy is a central obstacle to durable treatment. By defining which capsid mutations are forbidden and which allow escape, this work could guide capsid-targeting antivirals designed so that any escape mutation leaves the virus vulnerable to the patient's own innate immune proteins — an evolutionary trap rather than a target the virus can simply mutate past.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Hillel Haim
University of Iowa, IA·Microbiology & Immunology
Build a deep mutational scanning system using replication-defective HIV-1 to measure, safely and at high throughput, how every amino acid substitution at each site of the capsid protein affects viral fitness and resistance to the capsid inhibitor lenacapavir.
Masahiro Yamashita
Columbia University, NY·Microbiology & Immunology
Develop a high-throughput neutralization assay in which each HIV envelope (Env) variant in a lentiviral system carries a unique DNA barcode, allowing simultaneous tracking of hundreds of variants against ten broadly neutralizing antibodies targeting five gp120 sites.
Margaret J Lange
University of Missouri-Columbia, MO·Microbiology & Immunology
Identify new RNA aptamers, short structured nucleic acids selected for tight binding, that recognize additional HIV-1 capsid assembly forms, building toward a panel covering the lattice, hexamer and pentamer states.
The school
University of California-San Francisco: 89 labs on PI Pages, $2.1B a year on research, 164 research doctorates a year.
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