[The HIV nef and the Kaposi-sarcoma-associated virus K3/K5 proteins: "parasites"of the endocytosis pathway].
The modulation of plasma membrane proteins involved in the communication with the immune system is a general mechanism developed by viruses to escape the immune response. Most of the studied examples have focused on viral proteins that missort cellular proteins during their biosynthesis. However, an increasing number of examples show that the down-modulation can also be achieved after membrane delivery by targeting into the endocytic pathway. For both human immunodeficiency virus (HIV) and Kaposi sarcoma-associated herpesvirus (KSHV), the proteins required for this process are identified, Nef and K3/K5 respectively. The extensive studies in this field have shown that the mechanisms by which these proteins "parasite" the endocytic pathway are completely different. Nef directly interacts with components of the cellular machinery involved in the vesicular transport between the endocytic compartments, mainly the clathrin adaptor complexes (AP), inducing the misrouting of numerous cellular proteins, including CD4, MHC-I, LIGHT, DC-SIGN, CD28 and MHC-II to the endosomal degradation compartment or the trans Golgi-network. The K3 and K5 proteins from KSHV act by inducing the ubiquitylation of the target proteins, such as CMH-I and B7.2, triggering their internalization and subsequent degradation by the highly conserved Tsg101/vps23 ubiquitin-dependent endosomal pathway. While these findings show that the strategies used by viruses to target cellular proteins to the endocytic pathway are extremely diverse, additional investigations are needed for the complete understanding of the specific roles of Nef and K3/K5 in the physiopathology of HIV and KSHV infections, respectively. In addition, these viral factors represent valuable tools to study the pathway they are perturbing.
Bénichou
Serge
S
Département de Maladies Infectieuses, Inserm U.567, Cnrs UMR 8104, Institut Cochin, Bâtiment Gustave Roussy, 27, rue du Faubourg Saint-Jacques, 75014 Paris, France. benichou@cochin.inserm.fr
Benmerah
Alexandre
A
D020816:Amino Acid Motifs; D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000378:metabolism; D004705:Endocytosis; D018142:Gammaherpesvirinae / Q000235:genetics / Q000502:physiology; D015693:Gene Products, nef / Q000737:chemistry / Q000502:physiology*; D015754:Genes, nef; D015658:HIV Infections / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D019288:Herpesvirus 8, Human / Q000235:genetics / Q000502:physiology*; D006801:Humans; D017874:Immediate-Early Proteins / Q000737:chemistry / Q000502:physiology*; D046911:Macromolecular Substances; D051379:Mice; D009097:Multienzyme Complexes / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex; D011499:Protein Processing, Post-Translational; D021381:Protein Transport / Q000502:physiology*; D012514:Sarcoma, Kaposi / Q000276:immunology / Q000821:virology; D013329:Structure-Activity Relationship; D025801:Ubiquitin / Q000378:metabolism; D014764:Viral Proteins / Q000737:chemistry / Q000502:physiology*; D054311:nef Gene Products, Human Immunodeficiency Virus
D000954:Antigens, Surface; D015693:Gene Products, nef; D017874:Immediate-Early Proteins; C456022:K3 protein, Kaposi's sarcoma-associated herpesvirus; C405867:K5 protein, Human herpesvirus 8; D046911:Macromolecular Substances; D009097:Multienzyme Complexes; D025801:Ubiquitin; D014764:Viral Proteins; D054311:nef Gene Products, Human Immunodeficiency Virus; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex