Heat Shock Proteins: Role beyond Heat Stress
Author: Sachidanand Tiwari
Plants are constantly exposed to adverse environmental conditions. Alarming rate of global warming leads to abrupt occurrence of adverse meteorological fluctuations. Heat stress is one of major consequences of these seasonal variations. Due to sessile nature of plants, it should largely depend on its internal mechanism for tolerating external environment variations. Heat shock proteins play major role during heat stress exposure to plants. These conserved proteins are constitutive in expression and facilitate synthesis and folding of protein along with protein assembly and turnover. They play critical role in stabilizing unfolded or mis-folded protein during stress conditions as molecular chaperones, thus extend the cell time for repairing and resynthesizing new proteins. Thus HSP’s plays very important role for cell during stress conditions. During recent past years, deep insight in exploration of viral strategy shows interaction of small heat shock proteins with viral particles. Various studies confirmed about viral â€" induced chaperones expression in host organism facilitating in viral pathogenesis and stress alleviation. This interplay between chaperones and virus particles is very diverse and complex. This interplay can occur at different levels, including transcription, translation, post-translational modification, and cellular localization. Interaction between virus and HSP can occur through following means:
1. Cell entry and nuclear import â€" Entry of viruses are mediated by cell chaperones either through acting as a receptor signal for viruses or by helping in uncoating of viral capsid. This chaperones activity is noted for many plant and animal viruses like TMV, simian virus- 40, HIV. Hsp70 interact with viral proteins, alters their conformation resulting in import of viral genome in nucleus like import of reverse transcriptase enzyme.
2. Viral gene expression â€" Hsp90 promotes the activity of reverse transcriptase enzyme, involving in viral gene expression. Chaperones confirm conformational advantage to viral enzymes through their binding. This advantage may be due to bridging of two domain of RT enzymes or through stabilization of and activation of enzymes.
3. Protein folding and stability- Viral proteins are mainly depend upon endoplasmic reticulum for their protein folding. So ER chaperones (Bip and calcireticulin) greatly assist in folding of viral proteins. Chaperones help in maturation of virus coat protein, confirming its functional activity thus assist in assembly of mature virus particles.
In general molecular chaperones support protein folding / unfolding and assembly / disassembly reactions required for viral uncoating, membrane glycoprotein maturation, and nucleocapsid assembly and helps in maturation of viral particles.
Beside supportive action of HSP’s to viral infection, some action of HSP’s also assist in inducing resistance against viral infection strategies. Viruses reprogram the host immunity and apoptotic activity of cell. This programming induces immunity in cell through HSP’s action. HSP’s arrest cell division along with induction of innate immunity.
This complex interplay of molecular chaperones during viral infection is potentially exploited as a therapeutic strategies against viral infection. Use of Hsp 90 inhibitors like geldenamycin will prevent the maturation of viral particles, leads to aberrant folding, mislocalization and proteasomal degradation, thus is a very potent antiviral agent. Hsp 70 is also used as agent for developing innate and induced immunity against viruses. Extracellular HSP’s also induces immunity in plants against viral infection through induce immunity action.
References:
1. Viral interaction with molecular chaperones: role in regulating viral infection: Archives of virology â€" Page 1021-1031 - By A. Xiao, J. Wong, and H Luo.
2. Heat shock, stress proteins, chaperones, and proteotoxicity: Cell â€" Page 191- 197 â€" By L.E Hightower.
3. Virus-heat shock protein interaction and a novel axis for innate antiviral immunity: Cell â€" Page 646- 666 â€" By M.Y Kim and Oglesbee.
About Author / Additional Info:
I am currently pursuing Ph.D. in Biochemistry from Indian Agricultural Research Institute, New Delhi