Disease relevance of BPyVgp1

• The agnoprotein of simian virus 40 (SV40) is a 61-amino-acid protein encoded in the leader of some late mRNAs [1].
• A fourth late protein, agnoprotein, may contribute to the assembly of the virion [2].
• Reduced hr/hf progeny yields could result from decreased capsid protein synthesis and, in the absence of detectable levels of agnoprotein, from inefficient use of available capsid proteins [3].
• Expression of human neurotropic polyomavirus JCV late gene product agnoprotein in human medulloblastoma [4].
• The human polyomavirus JC virus (JCV) is the causative agent of a fatal demyelinating disease, progressive multifocal leukoencephalopathy, and encodes six major proteins, including agnoprotein [5].

High impact information on BPyVgp1

• BACKGROUND: The human neurotropic polyomavirus, JCV, contains an open reading frame within the late region of the viral genome that encodes a 71-amino-acid protein, agnoprotein [4].
• Because accumulating evidence supports an association between JCV infection and human brain tumors, including medulloblastomas, we assessed the presence of JCV Agno gene sequences and the expression of agnoprotein in a series of 20 well-characterized medulloblastomas [4].
• Studies were performed to verify the physiological significance of attenuation in the life cycle of simian virus 40 and the role of agnoprotein in this process [6].
• Agnoprotein colocalizes with microtubules in JCV-infected cells, but its function is not fully understood [5].
• These results suggest that FEZ1 promotes neurite extension through its interaction with microtubules, and that agnoprotein facilitates JCV propagation by inducing the dissociation of FEZ1 from microtubules [5].

Biological context of BPyVgp1

• Previous work showed that in CV1 cells infected with dl1066 and dl1140, levels of viral DNA replication and of late capsid protein accumulation were only slightly reduced and the failure to accumulate agnoprotein was not likely to be the major factor responsible for the mutants' growth defect [7].
• Of six independently isolated pseudorevertants, all had a missense mutation in a serine codon, near the beginning of the agnogene, that would cause replacement of serine at position 7, 11, or 17 in the agnoprotein by a hydrophobic amino acid [8].
• The agnoprotein reading frame, depending on how the mRNA precursor is spliced, is either not contained in the mRNA or is terminated near the VP2 AUG. Under these conditions, the ability of the agnoprotein AUG to block downstream CAT AUG utilization was found to be minimal in our assay [9].
• In this study, we investigated whether DNA elements located downstream of the JCV late promoter, encompassing the late leader peptide region, which encodes agnoprotein, play regulatory roles in the JCV lytic cycle [10].
• Here we demonstrate that in the absence of other viral proteins, expression of Agnoprotein can inhibit cell growth by deregulating cell progression through the cell cycle stages [11].

Anatomical context of BPyVgp1

• In similar analyses with stably transfected cell lines constitutively expressing the agnoprotein, VP1 localized to the nucleus before 30 h p.i., regardless of the infecting virus [1].
• Agnoprotein presented mostly in the infected oligodendrocytes and partly in the astrocytes [12].
• Biochemical and immunofluorescence analyses showed that Agno is targeted to the nuclear envelope and facilitates the nuclear egress of polyomavirus-like particles [13].
• The agnoprotein initiator codon and overlapping open reading frame thus act as strong barriers to further ribosome scanning and prevent initiation at the env AUG codon [14].
• Both procedures showed predominant localization of the agnoprotein to the cytosol and to the perinuclear region in association with the outer nuclear membrane [15].

Associations of BPyVgp1 with chemical compounds

• Here we report that agnoprotein expression sensitized cells to the cytotoxic effects of the DNA-damaging agent cisplatin [16].
• Moreover, conservative substitutions at PKC phosphorylation sites (Ser7, Ser11, and Thr21 to Asp) resulted in a viable virus, which further demonstrate the importance of these sites on agnoprotein function [17].
• Agnoprotein contains several potential phosphorylation sites, including Ser7, Ser11, and Thr21, which are potential targets for the serine/threonine-specific protein kinase C (PKC) [17].
• A leucine zipper-like motif present in agnoprotein 1a is considered to be involved in DNA binding [18].

Physical interactions of BPyVgp1

• Our results suggest that the agnoprotein interacts in a specific way with VP1 during the late stages of viral development [8].

Analytical, diagnostic and therapeutic context of BPyVgp1

• The antibody reacted with 8 kDa protein specific for JCV agnoprotein by Western blotting [12].
• Examination of 27 well-characterized clinical specimens by gene amplification and immunohistochemistry revealed the presence of DNA sequences corresponding to the JCV early genome and the late Agnoprotein in 22 samples and the JCV late genome encoding the viral capsid proteins in 8 samples [19].
• By indirect immunofluorescence, the agnoprotein was located predominantly in the cytoplasmic and perinuclear region of both cell lines; this is its site of localization in wild-type (WT)-infected CV-1P cells [20].
• Interaction between agnoprotein 1a and the major structural protein, VP1, was demonstrated by co-immunoprecipitation experiments using lysates of recombinant baculovirus-infected insect cells [18].

References