TY - JOUR
T1 - Adaptation of HIV-1 to rhTrim5α-mediated restriction in vitro
AU - Setiawan, Laurentia C.
AU - Kootstra, Neeltje A.
PY - 2015
Y1 - 2015
N2 - Recently, gene therapy with rhTrim5α, an innate restriction factor which blocks HIV-1 at a post entry step, have been shown to be applicable as treatment in vitro. However, HIV-1 might adapt to replicate in the presence of rhTrim5α due to its high mutation rate. Here we observed that two different HIV-1 isolates were able to replicate in cells expressing high levels of rhTrim5α. Escape mutations were found in the conserved regions of the viral genome, Gag and p51 RT subunit. Furthermore, the escape mutations, predominantly in the capsid and p51 RT, altered viral sensitivity to modified huTrim5α R332P and R335G variants, with only a minor effect on the replication capacity in primary PBMCs. Therefore, gene therapy with rhTrim5α might be suitable for HIV-1 treatment, however the virus will eventually escape the pressure by gaining mutations in the conserved regions of the viral genome without any severe fitness cost
AB - Recently, gene therapy with rhTrim5α, an innate restriction factor which blocks HIV-1 at a post entry step, have been shown to be applicable as treatment in vitro. However, HIV-1 might adapt to replicate in the presence of rhTrim5α due to its high mutation rate. Here we observed that two different HIV-1 isolates were able to replicate in cells expressing high levels of rhTrim5α. Escape mutations were found in the conserved regions of the viral genome, Gag and p51 RT subunit. Furthermore, the escape mutations, predominantly in the capsid and p51 RT, altered viral sensitivity to modified huTrim5α R332P and R335G variants, with only a minor effect on the replication capacity in primary PBMCs. Therefore, gene therapy with rhTrim5α might be suitable for HIV-1 treatment, however the virus will eventually escape the pressure by gaining mutations in the conserved regions of the viral genome without any severe fitness cost
U2 - https://doi.org/10.1016/j.virol.2015.09.017
DO - https://doi.org/10.1016/j.virol.2015.09.017
M3 - Article
C2 - 26469551
SN - 0042-6822
VL - 486
SP - 239
EP - 247
JO - Virology
JF - Virology
ER -