Raman
spectroscopy can be used as a tool to study virus entry and
pathogen-driven manipulation of the host efficiently. To date, Epstein–Barr
virus (EBV) entry and altered biochemistry of the glial cell upon
infection are elusive. In this study, we detected biomolecular changes
in human glial cells, namely, HMC-3 (microglia) and U-87 MG (astrocytes),
at two variable cellular locations (nucleus and periphery) by Raman
spectroscopy post-EBV infection at different time points. Two possible
phenomena, one attributed to the response of the cell to viral attachment
and invasion and the other involved in duplication of the virus followed
by egress from the host cell, are investigated. These changes corresponded
to unique Raman spectra associated with specific biomolecules in the
infected and the uninfected cells. The Raman signals from the nucleus
and periphery of the cell also varied, indicating differential biochemistry
and signaling processes involved in infection progression at these
locations. Molecules such as cholesterol, glucose, hyaluronan, phenylalanine,
phosphoinositide, etc. are associated with the alterations in the
cellular biochemical homeostasis. These molecules are mainly responsible
for cellular processes such as lipid transport, cell proliferation,
differentiation, and apoptosis in the cells. Raman signatures of these
molecules at distinct time points of infection indicated their periodic
involvement, depending on the stage of virus infection. Therefore,
it is possible to discern the details of variability in EBV infection
progression in glial cells at the biomolecular level using time-dependent in vitro Raman scattering.