Virus Details


VHFID6659

Host Factor Information

Gene Name COG4
HF Protein Name Conserved oligomeric Golgi complex subunit 4
HF Function Necessary for extracellular virus
Uniprot ID Q9H9E3
Protein Sequence View Fasta Sequence
NCBI Gene ID 25839
Host Factor (HF) Name in Paper COG4
Gene synonyms N.A.
Ensemble Gene ID ENSG00000103051
Ensemble Transcript ENST00000482252 [Q9H9E3-2]
KEGG ID Go to KEGG Database
Gene Ontology ID(s) GO:0000139, GO:0000301, GO:0006888, GO:0006890, GO:0007030, GO:0015031, GO:0017119, GO:0032588, GO:0042802, GO:0048213,
MINT ID Q9H9E3
STRING Click to see interaction map
GWAS Analysis Click to see gwas analysis
OMIM ID 606976
PANTHER ID N.A.
PDB ID(s) 3HR0,
pfam ID PF08318,
Drug Bank ID N.A.,
ChEMBL ID N.A.
Organism Homo sapiens (Human)

Pathogen Information

Virus Name Monkeypox virus
Virus Short Name MPV
Order Unassigned
Virus Family Poxviridae
Virus Subfamily Chordopoxvirinae
Genus Orthopoxvirus
Species Monkeypox virus
Host Human, mammals
Cell Tropism Dendritic cells, monocytes/macrophages, b lymphocytes, activated t lymphocytes
Associated Disease Similar to chickenpox
Mode of Transmission Respiratory, contact other
VIPR DB link https://www.viprbrc.org/brc/home.spg?decorator=pox
ICTV DB link https://talk.ictvonline.org/ictv-reports/ictv_9th_report/dsdna-viruses-2011/w/dsdna_viruses/74/poxviridae
Virus Host DB link http://www.genome.jp/virushostdb/view/?virus_lineage=Poxviridae

Publication Information

Paper Title Monkeypox Virus Host Factor Screen Using Haploid Cells Identifies Essential Role of GARP Complex in Extracellular Virus Formation
Author's Name Susan Realegeno, Andreas S. Puschnik, Amrita Kumar, Cynthia Goldsmith, Jillybeth Burgado, Suryaprakash Sambhara, Victoria A. Olson, Darin Carroll, Inger Damon, Tetsuya Hirata, Taroh Kinoshita, Jan E. Carette, Panayampalli Subbian Satheshkumar
Journal Name Journal Of Virology
Pubmed ID 28331092
Abstract Monkeypox virus (MPXV) is a human pathogen that is a member of the Orthopoxvirus genus, which includes Vaccinia virus and Variola virus(the causative agent of smallpox). Human monkeypox is considered an emerging zoonotic infectious disease. To identify host factors required for MPXV infection, we performed a genome-wide insertional mutagenesis screen in human haploid cells. The screen revealed several candidate genes, including those involved in Golgi trafficking, glycosaminoglycan biosynthesis, and glycosylphosphatidylinositol (GPI)-anchor biosynthesis. We validated the role of a set of vacuolar protein sorting (VPS) genes during infection, VPS51 to VPS54 (VPS51-54), which comprise the Golgi-associated retrograde protein (GARP) complex. The GARP complex is a tethering complex involved in retrograde transport of endosomes to the trans-Golgi apparatus. Our data demonstrate that VPS52 and VPS54 were dispensable for mature virion (MV) production but were required for extracellular virus (EV) formation. For comparison, a known antiviral compound, ST-246, was used in our experiments, demonstrating that EV titers in VPS52 and VPS54 knockout (KO) cells were comparable to levels exhibited by ST-246-treated wild-type cells. Confocal microscopy was used to examine actin tail formation, one of the viral egress mechanisms for cell-to-cell dissemination, and revealed an absence of actin tails in VPS52KO- or VPS54KO-infected cells. Further evaluation of these cells by electron microscopy demonstrated a decrease in levels of wrapped viruses (WVs) compared to those seen with the wild-type control. Collectively, our data demonstrate the role of GARP complex genes in double-membrane wrapping of MVs necessary for EV formation, implicating the host endosomal trafficking pathway in orthopoxvirus infection.IMPORTANCE Human monkeypox is an emerging zoonotic infectious disease caused by Monkeypox virus (MPXV). Of the two MPXV clades, the Congo Basin strain is associated with severe disease, increased mortality, and increased human-to-human transmission relative to the West African strain. Monkeypox is endemic in regions of western and central Africa but was introduced into the United States in 2003 from the importation of infected animals. The threat of MPXV and other orthopoxviruses is increasing due to the absence of routine smallpox vaccination leading to a higher proportion of naive populations. In this study, we have identified and validated candidate genes that are required for MPXV infection, specifically, those associated with the Golgi-associated retrograde protein (GARP) complex. Identifying host targets required for infection that prevents extracellular virus formation such as the GARP complex or the retrograde pathway can provide a potential target for antiviral therapy.
Used Model HAP1 and HEK297
DOI 10.1128/JVI.00011-17