Viral Proteins that Bridge Unconnected Proteins and Components in Human PPI Network - Molecular BioSystems (RSC Publishing)

Viruses, despite having small genomes and few proteins, make array of
interactions with host proteins as they solely depend on host machinery
for their replication and reproduction. Hence, analysis of Human-Virus
Protein-Protein Interaction Network (Hu-Vir PPI network) helps us to
gain certain insights into molecular mechanisms underlying hijacking of
host cell machinery by viruses for their perpetuation. Here we report an
analysis of Human-Virus Bridged PPI Network (HVBN) that has led us to
identify viral Articulation Points (VAPs) which connect unconnected
components of Human-PPI (Hu-PPI) network. VAPs cross-link peripheral
nodes to the giant component of Hu-PPI network. VAPs interact with
number of relatively lower topologically central human proteins and are
conserved among related viruses. The linked nodes comprise of those that
are mostly expressed during viral infection as well as those that are
found exclusively in some metabolic pathways indicating that these novel
viral mediation of certain human protein-protein interactions may form
basis for virus-specific tuning of host machinery. Functional importance
of VAPs and their interaction partners in virus replication make them
potential drug targets against viral infection. Our investigations also
lead to the discovery of an example of Human Endogenous Retrovirus
(HERV) encoded protein syncytin as an Articulation Point (AP) in Hu-PPI
network suggesting that the VAPs may get retained in a genome if they
result in any beneficial function to the host.