A novel cellular RNA helicase, RH116, differentially regulates cell growth, programmed cell death and human immunodeficiency virus type 1 replication.
In an effort to define novel cellular factors regulating human immunodeficiency virus type 1 (HIV-1) replication, a differential display analysis has been performed on endogenously infected cells stimulated with the HIV-suppressive immunomodulator Murabutide. In this study, the cloning and identification of a Murabutide-downregulated gene, named RH116, bearing classical motifs that are characteristic of the DExH family of RNA helicases, are reported. The 116 kDa encoded protein shares 99.9 % similarity with MDA-5, an inducible RNA helicase described recently. Ectopic expression of RH116 in HeLa-CD4 cells inhibited cell growth and cell proliferation but had no measurable effect on programmed cell death. RH116 presented steady state cytoplasmic localization and could translocate to the nucleus following HIV-1 infection. Moreover, the endogenous expression of RH116, at both the transcript and protein levels, was found to be considerably upregulated after infection. Overexpression of RH116 in HIV-1-infected HeLa-CD4 cells also resulted in a dramatic increase in the level of secreted viral p24 protein. This enhancement in virus replication did not stem from upregulated proviral DNA levels but correlated with increased unspliced and singly spliced viral mRNA transcripts. These findings implicate RH116 in the regulation of HIV-1 replication and point to an apoptosis-independent role for this novel helicase in inducing cell growth arrest.
Cocude
C
C
Laboratoire d'Immunologie Moléculaire de l'Infection et de l'Inflammation, Institut Pasteur de Lille, 1 Rue du Professeur Calmette, BP 245, 59019 Lille Cedex, France.
Truong
M-J
MJ
Laboratoire d'Immunologie Moléculaire de l'Infection et de l'Inflammation, Institut Pasteur de Lille, 1 Rue du Professeur Calmette, BP 245, 59019 Lille Cedex, France.
Billaut-Mulot
O
O
Laboratoire d'Immunologie Moléculaire de l'Infection et de l'Inflammation, Institut Pasteur de Lille, 1 Rue du Professeur Calmette, BP 245, 59019 Lille Cedex, France.
Delsart
V
V
Laboratoire d'Immunologie Moléculaire de l'Infection et de l'Inflammation, Institut Pasteur de Lille, 1 Rue du Professeur Calmette, BP 245, 59019 Lille Cedex, France.
Darcissac
E
E
Laboratoire d'Immunologie Moléculaire de l'Infection et de l'Inflammation, Institut Pasteur de Lille, 1 Rue du Professeur Calmette, BP 245, 59019 Lille Cedex, France.
Capron
A
A
Laboratoire d'Immunologie Moléculaire de l'Infection et de l'Inflammation, Institut Pasteur de Lille, 1 Rue du Professeur Calmette, BP 245, 59019 Lille Cedex, France.
Mouton
Y
Y
INSERM Unité 547, Institut Pasteur de Lille, 1 Rue du Professeur Calmette, BP 245, 59019 Lille Cedex, France.
Bahr
G M
GM
Laboratoire d'Immunologie Moléculaire de l'Infection et de l'Inflammation, Institut Pasteur de Lille, 1 Rue du Professeur Calmette, BP 245, 59019 Lille Cedex, France.
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000276:Adjuvants, Immunologic / Q000494:pharmacology; D020816:Amino Acid Motifs; D019380:Anti-HIV Agents / Q000494:pharmacology; D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes; D002470:Cell Survival / Q000187:drug effects; D003001:Cloning, Molecular; D053487:DEAD-box RNA Helicases; D018076:DNA, Complementary / Q000096:biosynthesis; D016655:HIV Core Protein p24 / Q000096:biosynthesis; D015497:HIV-1 / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D000072640:Interferon-Induced Helicase, IFIH1; D008969:Molecular Sequence Data; D008970:Molecular Weight; D020365:RNA Helicases / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D017386:Sequence Homology, Amino Acid; D020298:U937 Cells; D014779:Virus Replication / Q000187:drug effects
D000276:Adjuvants, Immunologic; D019380:Anti-HIV Agents; D018076:DNA, Complementary; D016655:HIV Core Protein p24; D000119:Acetylmuramyl-Alanyl-Isoglutamine; C033575:murabutide; C452815:IFIH1 protein, human; D053487:DEAD-box RNA Helicases; D000072640:Interferon-Induced Helicase, IFIH1; D020365:RNA Helicases