apl. Prof. Dr. Bar­bara Müller

barbara.mueller
(at)med.uni-heidelberg.de

Phone: +49 6221 56–1325
Fax: +49 6221 56–5003

Dynamic Events in HIV‑1 Replication

Projects

We are inter­est­ed in the biol­o­gy of retro­virus­es, in par­tic­u­lar the human immun­od­e­fi­cien­cy virus (HIV 1). With our work, we want to con­tribute to a detailed under­stand­ing of the intri­cate inter­ac­tions of this impor­tant pathogen with its host cell dur­ing the viral repli­ca­tion cycle.

The inter­ac­tion of a virus with its host cell is a high­ly dynam­ic process, involv­ing ordered and reg­u­lat­ed for­ma­tion, trans­port, trans­for­ma­tion and dis­so­ci­a­tion of (nucleo)protein com­plex­es. Bio­chem­i­cal, elec­tron micro­scop­ic and struc­tur­al stud­ies pro­vide detailed images of HI viri­ons and infor­ma­tion about the com­po­si­tion of func­tion­al­ly impor­tant sub­vi­ral com­plex­es. How­ev­er, these meth­ods yield snap­shots or ensem­ble data, which do not reflect the dynam­ics of indi­vid­ual events occur­ring in the infect­ed cell. In con­trast, mod­ern flu­o­res­cence imag­ing tech­niques enable us to direct­ly observe trans­port process­es and pro­tein inter­ac­tions with­in liv­ing cells. Fur­ther­more, super-res­o­lu­tion and cor­rel­a­tive microscopy now bridge the gap between elec­tron and light microscopy, allow­ing the visu­al­iza­tion of sub­vi­ral details via flu­o­res­cence microscopy. All these advanced imag­ing meth­ods require attach­ment of flu­o­res­cent labels to the viral pro­tein of interest.

Our aim is to ana­lyze dynam­ic process­es in HIV 1 repli­ca­tion in a quan­ti­ta­tive man­ner. For this, we devel­op flu­o­res­cent­ly labeled HIV 1 deriv­a­tives and flu­o­res­cent probes, which allow us to fol­low indi­vid­ual events in virus-cell inter­ac­tion with high time res­o­lu­tion. These stud­ies are com­bined with bio­chem­i­cal and viro­log­i­cal analy­ses. In our cur­rent work, we par­tic­u­lar­ly focus on the process­es involved in the for­ma­tion of the infec­tious HIV 1 cap­sid by assem­bly and pro­te­olyt­ic mat­u­ra­tion, and on the fate and role of this cap­sid struc­ture upon entry of the virus into a new host cell.

Respond­ing to the COVID-19 pan­dem­ic, we are also involved in the devel­op­ment of nov­el assay sys­tems and in sev­er­al clin­i­cal stud­ies. Although our main research field remains retro­vi­rol­o­gy, work on COVID-19 is cur­rent­ly continued.

Our main research inter­ests are:

  • HIV‑1 assem­bly and maturation
  • Dynam­ics of post-entry events in retro­vi­ral replication