HIV‑1 Infection and Latency


The Mücksch lab is inter­est­ed in gain­ing a bet­ter under­stand­ing of the inter­play between HIV‑1 and its host cells dur­ing HIV‑1 infec­tion and laten­cy at the cel­lu­lar and mol­e­c­u­lar lev­el. HIV infec­tion remains one of the world’s most rel­e­vant infec­tious dis­eases with more than 38 mil­lion peo­ple world­wide liv­ing with HIV. Since the begin­ning of the HIV epi­dem­ic, more than 84 mil­lion peo­ple have been infect­ed with HIV and about 40 mil­lion have died of HIV. Inten­sive research has led to the devel­op­ment of anti­retro­vi­ral ther­a­py (ART), which has since been applied to con­trol HIV infec­tion in peo­ple liv­ing with HIV. How­ev­er, despite avail­able ther­a­pies, HIV infec­tion still can­not be cured, result­ing in a need for life-long ART. This impos­es severe chal­lenges on peo­ple liv­ing with HIV, such as lim­it­ed access to ART, strict med­ica­tion sched­ule, stig­ma, side-effects, and inflam­ma­tion-asso­ci­at­ed co-mor­bidi­ties. The absence of a cure for HIV infec­tion results from the for­ma­tion of a latent reser­voir which can­not be tar­get­ed by cur­rent ther­a­pies. HIV inte­grates into the host cell genome where it can per­sist as a latent provirus dur­ing anti­retro­vi­ral treat­ment. Treat­ment inter­rup­tion inevitably leads to viral rebound. With this, the latent reser­voir presents the main chal­lenge to the devel­op­ment of a cure for HIV infec­tion and cure can thus only result from a detailed under­stand­ing of these process­es. The over­all aim of the Mücksch lab is to study and under­stand the mech­a­nisms under­ly­ing latent HIV‑1 infec­tion. Our research goals are to char­ac­ter­ize the het­ero­gene­ity of HIV‑1 laten­cy in cell mod­els and pri­ma­ry cells, inves­ti­gate how HIV enters and revers­es from laten­cy, and define the viral and host fac­tors respon­si­ble for these processes.

We believe that a process as het­ero­ge­neous and mul­ti-fac­to­r­i­al as HIV‑1 laten­cy can only be stud­ied using diverse tools and mod­els. We are apply­ing a provi­ral laten­cy reporter, which allows for rapid sep­a­ra­tion of cells har­bor­ing tran­scrip­tion­al­ly active vs. inac­tive provirus­es. This reporter enabled us to estab­lish excep­tion­al­ly large and diverse libraries of hun­dreds of latent­ly infect­ed T cell lines. Togeth­er with human pri­ma­ry cell mod­els, we are using these tools com­bined with mol­e­c­u­lar virol­o­gy, genet­ics, immunol­o­gy, and microscopy tech­niques to dis­sect HIV-host inter­ac­tions and under­stand the mech­a­nisms under­ly­ing laten­cy estab­lish­ment, main­te­nance, and rever­sal. Through this we expect to gain a bet­ter under­stand­ing of the reg­u­la­tion of HIV‑1 laten­cy to get one step clos­er to achiev­ing a cure for HIV.