Introduction: Human Herpesvirus 8 (HHV-8) causes classical, endemic (African), and Acquired
Immunodeficiency Syndrome (AIDS)-related Kaposi’s Sarcoma (KS), Body Cavity-Based Primary
Effusion Lymphomas (BCBL), HHV-8-associated peritoneal Primary Effusion Lymphoma
(PEL), and Multicentric Castleman’s Disease (MCD). HHV8 genome encodes several structural and
non-structural proteins, among which vIL6 is a functional homologue of Interleukin-6 (IL-6). It has
been established that vIL6 plays a vital role in HHV8 infections; also, it has been suggested that its
function was mediated through gp130, rather than the gp80 (IL-6 receptor [IL-6R]). This study aimed
to investigate the physicochemical and structural properties as well as the immunological features, and
finally the interaction between vIL6 and IL6 receptor (IL6R) by using several bioinformatics tools
which could provide both valuable insight into vIL6 protein and advantageous data for further studies
on HHV8 inhibitors and new vaccines.
Material and Methods: vIL6, human IL6 (hIL6), and IL6R were obtained from NCBI GenBank and
Uniport, which were aligned by The CLC Genomics Workbench. "Signal-BLAST" and “predisi" were
employed to define signal peptide; also, “Expasy’sProtParam” was used to predict physicochemical properties
as well as "DiANNA", and "SCRATCH" predicted the disulfide bonds. “NetPhosK”, “DISPHOS”,
“NetPhos”, ”NetNGlyc”, and ”GlycoEP” were involved to determine post-modification sites. To define
immunoinformatics analysis, “BcePred”, “ABCpred”, “Bepipred”, “AlgPred”, and "VaxiJen" were used.
“SOPMA”, “I-TASSER”, “GalaxyRefine”, and “3D-Refine” predicted and refined the secondary and tertiary
structures. TM-align server was used to align 3D structures. In addition, docking analysis was done
by “Hex 5.0.”, and finally the results were illustrated by “Discovery Studio”.
Results: A signal peptide (1-22) was defined in the vIL6 sequences and analysis has shown that vIL6
is an acidic protein which is significantly stable in all organisms. Three Disulfide bonds were predicted
and immunoinformatics analysis showed 5 distinct B-cell epitopes. vIL6 is predicted as a non-allergen
protein and the majority of its structure consists of Alpha helix. TM-align pointed the significant similarity
between vIL6 and hIL6 in protein folding. The high energy value between vIL6 protein and
IL6R was calculated and further analysis illustrated 5 conserved regions as well as 4 conserved amino
acids which had a significant role in vIL6 and IL6R interaction.
Discussion: An in silico study by numerous software determined the possible interaction between vIL6
and IL6R and the possible role of this interaction in HHV8 pathogenesis and the progress of infection.
These have been overlooked by previous studies and will be beneficial to gain a more comprehensive
understanding of vIL6 function during HHV8 lifecycle and infections. Structural analysis showed the
significant similarity between vIL6 and hIL6 folding which can describe the similarity of the functions
or interactions of both proteins. Furthermore, several conserved regions in the interaction site which
interestingly were highly conserved among all vIL6 sequences can be used as new target for vIL6 inhibitors.
Moreover, our results could predict immunological properties of vIL6 which suggested the
ability of this protein in induction of the humoral immune response. Such a protein may be used for
further studies on therapeutic vaccine fields.