Interaction of Vpx and apolipoprotein B mRNA-editing catalytic polypeptide 3 family member A (APOBEC3A) correlates with efficient lentivirus infection of monocytes.
The accessory protein Vpx is encoded by lentiviruses of the human immunodeficiency virus type 2 (HIV-2) and the simian immunodeficiency SIVsm/SIVmac lineage. It is packaged into virions and is indispensable in early steps of monocyte infection. HIV-1, which does not encode Vpx, is not able to infect human monocytes, but Vpx enables infection with HIV-1. The underlying mechanism is not completely understood. In this work, we focus on Vpx-mediated intracellular postentry events as counteraction of host cell proteins. We found that Vpx binds to apolipoprotein B mRNA-editing catalytic polypeptide 3 family member A (APOBEC3A; A3A), a member of the family of cytidine deaminases, present in monocytes. This interaction led to a reduction of the steady-state protein level of A3A. A single-point mutation in Vpx (H82A) abrogated binding to A3A and single-round infection of monocytes by HIV-1. Taken together, our data indicate that lentiviral Vpx counteracts A3A in human monocytes.
Berger
André
A
Division of Medical Biotechnology, Paul-Ehrlich-Institut, 63225 Langen, Germany.
Münk
Carsten
C
Schweizer
Matthias
M
Cichutek
Klaus
K
Schüle
Silke
S
Flory
Egbert
E
D002460:Cell Line; D003564:Cytidine Deaminase / Q000378:metabolism*; D015658:HIV Infections / Q000209:etiology / Q000378:metabolism / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity*; D006367:HeLa Cells; D006801:Humans; D009000:Monocytes / Q000378:metabolism* / Q000821:virology*; D016297:Mutagenesis, Site-Directed; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism*; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity*; D014162:Transfection; D054334:Viral Regulatory and Accessory Proteins / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication / Q000235:genetics / Q000502:physiology
D011506:Proteins; C513059:VPX protein, Simian immunodeficiency virus; D054334:Viral Regulatory and Accessory Proteins; C121399:APOBEC3A protein, human; D003564:Cytidine Deaminase