Persistent transcription of a nonintegrating mutant of simian immunodeficiency virus in rhesus macrophages

@article{citeulike:2499831, abstract = {A nonintegrating mutant, SIVsmD116N, was derived from the infectious pathogenic SIVsmE543-3 clone by introducing an Asp (D) to Asn (N) mutation into the catalytic domain of integrase. Although SIVsmD116N generated all viral proteins following transfection, cell-free virus did not productively infect CEMx174 cells, macaque peripheral blood mononuclear cells (PBMCs) or monocyte-derived macrophages (MDM). Viral DNA and transcripts were observed transiently in SIVsmD116N-infected CEMx174 cells and macaque PBMC but persisted in MDM for as long as 20 days. Circular forms of viral DNA were detected but there was no evidence of integration detected by Alu PCR. We found that SIV D116N mutant remained transcriptionally active and expressed low levels of viral proteins persistently in MDM. These data are consistent with a role for macrophages as a persistent latent reservoir for AIDS viruses. The capacity of nonintegrating SIV to persistently generate viral products in macrophages suggests that nonintegrating lentiviral vectors could be engineered to efficiently and safely express proteins for vaccine purposes.}, author = {Zheng, Yanfang and Ourmanov, Ilnour and Hirsch, Vanessa M. }, citeulike-article-id = {2499831}, doi = {http://dx.doi.org/10.1016/j.virol.2007.11.002}, journal = {Virology}, keywords = {hiv, macrophage, replication}, month = {March}, number = {2}, pages = {291--299}, posted-at = {2008-03-10 09:48:17}, priority = {2}, title = {Persistent transcription of a nonintegrating mutant of simian immunodeficiency virus in rhesus macrophages}, url = {http://dx.doi.org/10.1016/j.virol.2007.11.002}, volume = {372}, year = {2008} }

TY - JOUR ID - citeulike:2499831 L3 - citeulike-article-id:2499831 TI - Persistent transcription of a nonintegrating mutant of simian immunodeficiency virus in rhesus macrophages JF - Virology VL - 372 IS - 2 SP - 291 EP - 299 N2 - A nonintegrating mutant, SIVsmD116N, was derived from the infectious pathogenic SIVsmE543-3 clone by introducing an Asp (D) to Asn (N) mutation into the catalytic domain of integrase. Although SIVsmD116N generated all viral proteins following transfection, cell-free virus did not productively infect CEMx174 cells, macaque peripheral blood mononuclear cells (PBMCs) or monocyte-derived macrophages (MDM). Viral DNA and transcripts were observed transiently in SIVsmD116N-infected CEMx174 cells and macaque PBMC but persisted in MDM for as long as 20 days. Circular forms of viral DNA were detected but there was no evidence of integration detected by Alu PCR. We found that SIV D116N mutant remained transcriptionally active and expressed low levels of viral proteins persistently in MDM. These data are consistent with a role for macrophages as a persistent latent reservoir for AIDS viruses. The capacity of nonintegrating SIV to persistently generate viral products in macrophages suggests that nonintegrating lentiviral vectors could be engineered to efficiently and safely express proteins for vaccine purposes. KW - hiv KW - macrophage KW - replication AU - Zheng, Yanfang AU - Ourmanov, Ilnour AU - Hirsch, Vanessa PY - 2008/03/15/ UR - http://dx.doi.org/10.1016/j.virol.2007.11.002 ER -