Prediction of HIV-1 virus-host protein interactions using virus and host sequence motifs

Abstract

Background: Host protein-protein interaction networks are altered by invading virus proteins, which create new interactions, and modify or destroy others. The resulting network topology favors excessive amounts of virus production in a stressed host cell network. Short linear peptide motifs common to both virus and host provide the basis for host network modification.

The Road Less Traveled: HIV's Use of Alternative Routes through Cellular Pathways

“…Analysis of PPI structural data revealed that virus-host interacting interfaces bury smaller surface areas (ϳ950 Å 2 ) than internal cellular interactions (ϳ1,780 Å 2 ) (40). Of course, the weaker virushost PPIs must compete with the stronger host-host PPIs, and this is apparently achieved with sheer numbers, since the high copy number of viral proteins in the infected cell can push the equilibrium toward the virus-host interaction (53). The origin of the weaker virus-host interactions is probably a result of viral protein evolution toward supporting flexible interactions with various partners.…”

“…The late assembly domains (PTAP and YPXL of HIV-1 Gag-p6) mimic comparable cellular interfaces in the exploitation of the cellular ESCRT pathway of membrane fission (e.g., Gag PTAP mimics cellular HRS protein in binding the UEV domain of TSG101) (37,38). Given their functional essentiality, these short motifs are highly conserved (11,52,53), function independently of their location within the targeting protein, and can be functionally exchanged with comparable motifs from other proteins (39,55).…”

“…Short linear peptide motifs common to both virus and host proteins have been suggested to provide the basis for host PPI network hijacking (11,52,53). The motif basis of such PPIs is not restricted to a single pathogen protein but is widely distributed across the proteome of HIV-1, including Nef, Env, Tat, Rev, Vif, and Vpu (53). For example, HIV-1 Vif binds host Elongin-B and Elongin-C (Elongin-B/C) proteins through its short BC-box motif (SLQYLA), which mimics the conserved cellular interface of SOCS-box proteins (reviewed in reference 54).…”

Functions of Tat: the versatile protein of human immunodeficiency virus type 1

“…Normal cell functioning of viral hosts is altered by invading virus proteins to the benefit of the virus (Evans et al, 2009). Viral proteins are known to compete with the host proteins thus disrupting the normal host protein-protein interaction network (Sodhi et al, 2004;Tournier & Quesnel-Hellmann, 2006).…”

Differential Expression of Rac-1, Cxcr4 and CCR5 on CD4 T-Cells at Different Stages of HIV-1 Disease Relate To Its Progression in Therapy Naive Individuals

“…Normal cell functioning of host is altered by invading viral proteins to the benefit of the virus [11]. There have been constant efforts to understand these interactions between viral and cellular gene products which together determine the host's susceptibility to infection and disease progression in HIV-1 infection [12].…”