Innate sensing and cellular restriction factors targeting endogenous retroviruses and HIV‑1

Project Member

Prof. Dr. Nor­bert Ban­nert

Project Leader

Prof. Dr. Norbert Bannert

Phone: +49 30 18754 – 2549
Fax: +49 30 18754 – 2334
BannertN@rki.de

Head of Divi­sion for HIV
and oth­er Retro­virus­es
Robert Koch Insti­tute
Nor­dufer 20
13353 Berlin
Ger­many

Dr. Oya Cingöz

Project Leader

Dr. Oya Cingöz

CingoezO@rki.de

Divi­sion for HIV and oth­er Retro­virus­es
Robert Koch Insti­tute
Nor­dufer 20
13353 Berlin
Ger­many

Adri­ana Block,
PhD Stu­dent

Nico­las Arnow,
PhD Stu­dent

Project Summary

Cells are con­front­ed with new infec­tions by exoge­nous retro­virus­es as well as with expres­sion of endoge­nous retro­virus­es resid­ing in their own genomes. There are cel­lu­lar coun­ter­mea­sures in place that func­tion to pro­tect the host against such pathogens; in par­tic­u­lar the mul­ti­ple innate immune sig­nal­ing path­ways that rec­og­nize and respond to var­i­ous mol­e­c­u­lar pat­terns asso­ci­at­ed with these virus­es. In case of Human Endoge­nous Retro­virus­es (HERV), such respons­es have been asso­ci­at­ed with autoim­mune dis­eases and pro­tec­tion from can­cers. In case of HIV‑1 infec­tion, chron­ic immune acti­va­tion is one of the hall­marks of a detri­men­tal cycle con­sist­ing of viral repli­ca­tion and pro­longed inflam­ma­tion, ulti­mate­ly result­ing in the loss of func­tion­al immune cells.

Whether endoge­nous and exoge­nous retro­virus­es are sub­ject to innate immune sens­ing in infect­ed cells, and if so, when and where this response occurs remains a top­ic of dis­cus­sion. Thus far, every pos­si­ble step of the retro­vi­ral repli­ca­tion cycle has been pro­posed to stim­u­late innate immune respons­es. We and oth­ers dis­cov­ered that infec­tion of human mono­cyte-derived macrophages with HIV‑1 or HIV‑2 results in strong stim­u­la­tion of innate immune acti­va­tion in the pres­ence, but not in the absence of Vpx. The anti­retro­vi­ral gene prod­ucts and sens­ing path­ways act­ing against endoge­nous retro­virus­es like HERVs remain large­ly unknown. We inves­ti­gate the viral and cel­lu­lar deter­mi­nants of innate immune induc­tion against HIV‑1 and HERVs, as well as cel­lu­lar restric­tions pre­vent­ing HERV pro­lif­er­a­tion. Impli­ca­tions of the sens­ing response to cells of the innate immune sys­tem is anoth­er focus of the project.

Fig. 1: Thin sec­tion elec­tron microscopy of recon­sti­tut­ed HERVK(HML2) par­ti­cles
(Chu­dak et al. Retro­vi­rol­o­gy, 2013).

Fig. 2: Innate immune recog­ni­tion of HIV‑1 (Iwasa­ki A., Immu­ni­ty, 2012).