title: Molecules from apoptotic pathways modulate HIV-1 replication in Jurkat cells.
abstract: The replication of viruses involves control of some aspects of host cell homeostasis by modification of target cell metabolism and regulation of the apoptotic machinery. It is not well known whether molecules involved in apoptotic pathways affect human immunodeficiency virus type 1 (HIV-1) replication and regulate viral yields. Using the susceptible Jurkat cell line, we studied the relationship of apoptosis-associated molecules with HIV-1 virus production using a sensitive real-time RT-PCR assay. Here, we found that expression of proapoptotic proteins, including Fas ligand (FasL), FADD, or p53 significantly increased HIV-1 virus production. In contrast, the expression of antiapoptotic molecules, such as FLIP, Bcl-X(L), and XIAP, decreased HIV-1 virus production. Knockdown of Bax with siRNA and FADD with expression of its antisense mRNA also inhibited viral replication and the caspase-3 inhibitor, Z-DEVD, and decreased virus production. These data indicate that HIV-1 infection regulates the apoptosis process to facilitate viral replication and inhibition of apoptosis may inhibit HIV-1 replication and cytopathogenesis. We also discuss the effects of MAPK signaling pathways and apoptosis on HIV-1 replication.
authors.affiliation: Laboratory of Molecular Virology, Division of Emerging and Transfusion Transmitted Diseases, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA. xue.wang@fda.hhs.gov
authors.forename: Xue
authors.initials: X
authors.lastname: Wang
authors.forename: Viswanath
authors.initials: V
authors.lastname: Ragupathy
authors.forename: Jiangqin
authors.initials: J
authors.lastname: Zhao
authors.forename: Indira
authors.initials: I
authors.lastname: Hewlett
mesh_terms: D017209:Apoptosis; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein / Q000096:biosynthesis; D003588:Cytopathogenic Effect, Viral; D053222:Fas Ligand Protein / Q000096:biosynthesis; D053200:Fas-Associated Death Domain Protein / Q000096:biosynthesis / Q000235:genetics; D055785:Gene Knockdown Techniques; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D019169:Jurkat Cells; D034741:RNA, Small Interfering / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis; D014779:Virus Replication; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000096:biosynthesis; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis / Q000235:genetics; D051020:bcl-X Protein / Q000096:biosynthesis
chemical_list: D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; C505533:FADD protein, human; D053222:Fas Ligand Protein; D053200:Fas-Associated Death Domain Protein; D034741:RNA, Small Interfering; D016159:Tumor Suppressor Protein p53; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein