SARS-CoV 7b protein does not seem to have any role in virus
pathogenesis or replication as a deletion mutant simultaneously
missing genes 6, 7a, 7b, 8a, 8b and 9b (SARS-CoV Δ6-9b) showed
similar virus replication rates and caused pathogenesis similar to the
wild type virus [74]. However, SARS-CoV 7b protein PBM is not
present in SARS-CoV variants isolated from bats, in contrast to
viruses isolated from civet cats and humans, indicating that 7b
protein PBM could be involved in virus adaptation, similarly to
the PBMs of E and 3a proteins [75].
To further explore the relevance of CoV PBMs and their
involvement in virus replication and pathogenesis, the cellular
PDZ binding partners of these viral PBMs need to be identified.
To this end, a yeast-two hybrid assay was performed in which the
highly pathogenic human CoV, SARS-CoV and MERS-CoV, PBMs
were used as bait and the 266 human cellular PDZ domains were
used as prey (Fig. 3). It was observed that SARS-CoV and MERSCoV E protein PBMs bind cellular PDZ proteins involved in the
regulation of NfκB pathway, one of the hallmarks of SARS-CoV
pathogenesis [76], potentially contributing to virus virulence
Table 3
PBMs conserved in MERS-CoV and MERS-CoV isolated from animals
VIRAL
PROTEIN
VIRUS
HOST
Nº ISOLATES
PBM
SARS-CoV E
PROTEIN
SARS-CoV
Human
>100
…NLNSSEGVPDDLV
SARS-CoV
Civet Cats
>20
…NLNSSEGVPDDLV
SARS-CoV Like
Bats R. pusillus
1
…NLNSSVGVPDDLV
SARS-CoV Like
Bats R.
ferrumequinum
1
…NLNSSDCVPDDLV
SARS-CoV Like
Bats R. blasii
1
…SLNSSQEVPEFLV
MERS-CoV E
PROTEIN
MERS-CoV
Human
98
…QDSKPPLPPDEWV
MERS-CoV
Dromedary
17
…QDSKPPLPPDEWV
MERS-CoV-Like
Bats N. capensis
1
…QESKPPLPPEEWV
MERS-CoV-Like
Bats V. superans
1
…QESKPPLPPDEWV
MERS-CoV-Like HKU5
Bats Pipistrellus
6
…QESHPPYPPEDWV
MERS-CoV-Like-HKU4
Bats T. pachypus
7
…QENRPPFPPEDWV
SARS-CoV
3a PROTEIN
SARS-CoV
Human
166
…IYDEPTTTTSVPL
SARS-CoV
Human
3
…IYDEPMTTTSVPL
SARS-CoV
Civet Cats
4
…IYDEPTTTTSVPL
SARS-CoV-Like
Bats R. sinicus
1
…IYDEPMTTTSVPL
Zaria Bat-CoV
H. commersoni
1
…IYDEPPTTTSVPL
MERS-CoV 5
PROTEIN
MERS-CoV
Human
97
…VPLHIIAPSLIV
MERS-CoV
Dromedary
17
…VPLHIIAPSLIV
MERS-CoV-Like
Bats N. capensis
1
…VPLHIIAPVLSV
MERS-CoV-Like
Bats V. superans
1
…VPLHIIAPVLSV
MERS-CoV-Like HKU5
Bats Pipistrellus
6
…VPLHIIAPVLTV
MERS-CoV-Like-HKU4
Bats T. pachypus
7
…VPLHIIAPKLYV
230
Carlos Castan ˜ o-Rodriguez et al.
pathogenesis or replication as a deletion mutant simultaneously
missing genes 6, 7a, 7b, 8a, 8b and 9b (SARS-CoV Δ6-9b) showed
similar virus replication rates and caused pathogenesis similar to the
wild type virus [74]. However, SARS-CoV 7b protein PBM is not
present in SARS-CoV variants isolated from bats, in contrast to
viruses isolated from civet cats and humans, indicating that 7b
protein PBM could be involved in virus adaptation, similarly to
the PBMs of E and 3a proteins [75].
To further explore the relevance of CoV PBMs and their
involvement in virus replication and pathogenesis, the cellular
PDZ binding partners of these viral PBMs need to be identified.
To this end, a yeast-two hybrid assay was performed in which the
highly pathogenic human CoV, SARS-CoV and MERS-CoV, PBMs
were used as bait and the 266 human cellular PDZ domains were
used as prey (Fig. 3). It was observed that SARS-CoV and MERSCoV E protein PBMs bind cellular PDZ proteins involved in the
regulation of NfκB pathway, one of the hallmarks of SARS-CoV
pathogenesis [76], potentially contributing to virus virulence
Table 3
PBMs conserved in MERS-CoV and MERS-CoV isolated from animals
VIRAL
PROTEIN
VIRUS
HOST
Nº ISOLATES
PBM
SARS-CoV E
PROTEIN
SARS-CoV
Human
>100
…NLNSSEGVPDDLV
SARS-CoV
Civet Cats
>20
…NLNSSEGVPDDLV
SARS-CoV Like
Bats R. pusillus
1
…NLNSSVGVPDDLV
SARS-CoV Like
Bats R.
ferrumequinum
1
…NLNSSDCVPDDLV
SARS-CoV Like
Bats R. blasii
1
…SLNSSQEVPEFLV
MERS-CoV E
PROTEIN
MERS-CoV
Human
98
…QDSKPPLPPDEWV
MERS-CoV
Dromedary
17
…QDSKPPLPPDEWV
MERS-CoV-Like
Bats N. capensis
1
…QESKPPLPPEEWV
MERS-CoV-Like
Bats V. superans
1
…QESKPPLPPDEWV
MERS-CoV-Like HKU5
Bats Pipistrellus
6
…QESHPPYPPEDWV
MERS-CoV-Like-HKU4
Bats T. pachypus
7
…QENRPPFPPEDWV
SARS-CoV
3a PROTEIN
SARS-CoV
Human
166
…IYDEPTTTTSVPL
SARS-CoV
Human
3
…IYDEPMTTTSVPL
SARS-CoV
Civet Cats
4
…IYDEPTTTTSVPL
SARS-CoV-Like
Bats R. sinicus
1
…IYDEPMTTTSVPL
Zaria Bat-CoV
H. commersoni
1
…IYDEPPTTTSVPL
MERS-CoV 5
PROTEIN
MERS-CoV
Human
97
…VPLHIIAPSLIV
MERS-CoV
Dromedary
17
…VPLHIIAPSLIV
MERS-CoV-Like
Bats N. capensis
1
…VPLHIIAPVLSV
MERS-CoV-Like
Bats V. superans
1
…VPLHIIAPVLSV
MERS-CoV-Like HKU5
Bats Pipistrellus
6
…VPLHIIAPVLTV
MERS-CoV-Like-HKU4
Bats T. pachypus
7
…VPLHIIAPKLYV
230
Carlos Castan ˜ o-Rodriguez et al.