through viral proteins including a PBM (Table 1). Given the functional versatility of proteins including PDZ domains, viruses deregulate a wide range of cellular functions through their PBMs
modulating viral replication and dissemination, and contributing
to viral pathogenesis. In some cases, viral PBMs interact with
cellular PDZs contributing to their degradation or inactivation
and in others, they cause their activation or change their function
by subcellular relocalization [16, 17]. The first viral PBMs were
identified two decades ago in viral oncoproteins, like human papillomavirus (HPV) E6 protein, or human T-cell lymphotropic virus
type I (HTLV-1) tax protein [18, 19] or, more recently, Hepatitis C
virus (HCV) NS4b protein [20]. Furthermore, viral PBMs have
also been described in proteins from nononcogenic viruses, such as
proteins NS1 from influenza virus, NS5 from Tick-borne Encephalitis Virus (TBEV), or SARS-CoV E protein [21–23].
The diversity among the viral PBMs could be similar to that of
the cellular ones as some internal viral PBMs or viral proteins
containing both a PDZ domain and a PBM have been identified.
As an example, TBEV NS5 protein has two PBMs: one located in its
carboxy terminus end, similarly to its homolog proteins from other
flaviviruses such as Dengue Virus (DENV) or West Nile Virus
(WNV), and an internal PBM in its MTase domain [21]. Also,
F11 protein of vaccinia virus has both a PBM and a PDZ domain,
and the two of them are effectively coordinated to promote viral
dissemination [24].
In this chapter we will review how viral PBMs target relevant
cellular processes governed by cellular proteins including PDZ
domains: cell–cell junctions, polarity, and survival/apoptosis.
Also, the influence of these viral PBMs on the host immune system
contributing to viral pathogenicity will be discussed. In the last part
of the review the focus will be set on the PBMs in CoVs proteins,
their conservation through evolution and how they influence viral
replication and pathogenicity.
2 Cellular Processes Targeted by Viral PBMs
Viruses have adopted many strategies throughout evolution to use
the cellular machinery for their own biological processes as well as
to counteract host defenses. The best-known cellular processes
affected by viral PBMs are cell–cell junction formation, cell polarity
establishment, the regulation of cellular proliferation/apoptosis
and of the immune system. For a clearer understanding of how
viral PBMs work, it is worthy to focus on each of these processes
one by one.
PBM-PDZ Interactions and Viral Pathogenesis
221
modulating viral replication and dissemination, and contributing
to viral pathogenesis. In some cases, viral PBMs interact with
cellular PDZs contributing to their degradation or inactivation
and in others, they cause their activation or change their function
by subcellular relocalization [16, 17]. The first viral PBMs were
identified two decades ago in viral oncoproteins, like human papillomavirus (HPV) E6 protein, or human T-cell lymphotropic virus
type I (HTLV-1) tax protein [18, 19] or, more recently, Hepatitis C
virus (HCV) NS4b protein [20]. Furthermore, viral PBMs have
also been described in proteins from nononcogenic viruses, such as
proteins NS1 from influenza virus, NS5 from Tick-borne Encephalitis Virus (TBEV), or SARS-CoV E protein [21–23].
The diversity among the viral PBMs could be similar to that of
the cellular ones as some internal viral PBMs or viral proteins
containing both a PDZ domain and a PBM have been identified.
As an example, TBEV NS5 protein has two PBMs: one located in its
carboxy terminus end, similarly to its homolog proteins from other
flaviviruses such as Dengue Virus (DENV) or West Nile Virus
(WNV), and an internal PBM in its MTase domain [21]. Also,
F11 protein of vaccinia virus has both a PBM and a PDZ domain,
and the two of them are effectively coordinated to promote viral
dissemination [24].
In this chapter we will review how viral PBMs target relevant
cellular processes governed by cellular proteins including PDZ
domains: cell–cell junctions, polarity, and survival/apoptosis.
Also, the influence of these viral PBMs on the host immune system
contributing to viral pathogenicity will be discussed. In the last part
of the review the focus will be set on the PBMs in CoVs proteins,
their conservation through evolution and how they influence viral
replication and pathogenicity.
2 Cellular Processes Targeted by Viral PBMs
Viruses have adopted many strategies throughout evolution to use
the cellular machinery for their own biological processes as well as
to counteract host defenses. The best-known cellular processes
affected by viral PBMs are cell–cell junction formation, cell polarity
establishment, the regulation of cellular proliferation/apoptosis
and of the immune system. For a clearer understanding of how
viral PBMs work, it is worthy to focus on each of these processes
one by one.
PBM-PDZ Interactions and Viral Pathogenesis
221