Characterization of entry and infection of monocytic THP-1 cells by Kaposi's sarcoma associated herpesvirus (KSHV): role of heparan sulfate, DC-SIGN, integrins and signaling.
KSHV effectively binds, enters and establishes infection in THP-1 cells with initial concurrent expression of latent ORF73 and lytic ORF50 genes and subsequent persistence of ORF73. KSHV genome persisted for 30 days and lytic cycle could be activated. KSHV utilized heparan sulfate for binding to THP-1 cells and primary monocytes. Blocking DC-SIGN did not inhibit KSHV binding; however, virus entry in THP-1 cells and in primary monocytes was reduced. In addition to the previously identified integrins alpha3beta1, alphavbeta3 and alphavbeta5, integrin alpha5beta1 was also utilized for infection. KSHV entered THP-1 cells via clathrin and caveolin mediated endocytosis and did not utilize macropinocytosis as in human dermal endothelial cells, and required an endosomal acidification. Infection also induced phosphorylation of FAK, Src, PI3K, NF-kappaB and ERK1/2 signaling molecules, and entry was blocked by tyrosine kinase inhibitors. These findings suggest that THP-1 cells are highly useful model for studying KSHV infection of monocytes.
Kerur
Nagaraj
N
H. M. Bligh Cancer Research Laboratories, Department of Microbiology and Immunology, Chicago Medical School, Rosalind Franklin University of Medicine and Science, 3333 Green Bay Road, North Chicago, IL 60064, USA.
Veettil
Mohanan Valiya
MV
Sharma-Walia
Neelam
N
Sadagopan
Sathish
S
Bottero
Virginie
V
Paul
Arun George
AG
Chandran
Bala
B
D000956:Antigens, Viral / Q000235:genetics; D015815:Cell Adhesion Molecules / Q000502:physiology*; D002460:Cell Line; D002467:Cell Nucleus / Q000821:virology; D004279:DNA, Viral / Q000235:genetics / Q000378:metabolism; D004705:Endocytosis / Q000502:physiology; D015870:Gene Expression; D006497:Heparan Sulfate / Q000502:physiology*; D019288:Herpesvirus 8, Human / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology*; D054884:Host-Pathogen Interactions / Q000502:physiology; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics; D016023:Integrins / Q000502:physiology*; D007700:Kinetics; D037181:Lectins, C-Type / Q000502:physiology*; D009000:Monocytes / Q000502:physiology / Q000821:virology*; D009687:Nuclear Proteins / Q000235:genetics; D011956:Receptors, Cell Surface / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D015534:Trans-Activators / Q000235:genetics; D053586:Virus Internalization; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D000956:Antigens, Viral; D015815:Cell Adhesion Molecules; D004279:DNA, Viral; D006497:Heparan Sulfate; D017874:Immediate-Early Proteins; D016023:Integrins; D037181:Lectins, C-Type; D009687:Nuclear Proteins; D011956:Receptors, Cell Surface; D015534:Trans-Activators; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C417604:Rta protein, Human herpesvirus 8; C109540:latency-associated nuclear antigen