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How Polyomaviruses Exploit the ERAD Machinery to Cause Infection

View Article: PubMed Central - PubMed

ABSTRACT

To infect cells, polyomavirus (PyV) traffics from the cell surface to the endoplasmic reticulum (ER) where it hijacks elements of the ER-associated degradation (ERAD) machinery to penetrate the ER membrane and reach the cytosol. From the cytosol, the virus transports to the nucleus, enabling transcription and replication of the viral genome that leads to lytic infection or cellular transformation. How PyV exploits the ERAD machinery to cross the ER membrane and access the cytosol, a decisive infection step, remains enigmatic. However, recent studies have slowly unraveled many aspects of this process. These emerging insights should advance our efforts to develop more effective therapies against PyV-induced human diseases.

No MeSH data available.


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Simian virus 40 (SV40) structure and entry pathway. (A) SV40 consists of 360 VP1 copies arranged as 72 pentamers, which are localized on the viral surface. The pentamers are stabilized by disulfide bonds, as well as by interactions between the VP1 carboxy-terminus, which invades a neighboring pentamer (black curved lines). VP1 also binds to the underlying internal hydrophobic proteins VP2 and VP3. (B) To infect cells, SV40 interacts with the glycolipid receptor ganglioside GM1 on the plasma membrane, internalizes, and traffics to the endolysosomes (step 1). The virus then targets to the endoplasmic reticulum (ER) using a lipid-sorting mechanism (step 2), from where it crosses the ER membrane to access the cytosol (step 3). Upon entering the cytosol, SV40 mobilizes into the nucleus (step 4), where ensuing transcription and replication of the viral genome causes lytic infection or cellular transformation. NPC: nuclear pore complex.
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viruses-08-00242-f001: Simian virus 40 (SV40) structure and entry pathway. (A) SV40 consists of 360 VP1 copies arranged as 72 pentamers, which are localized on the viral surface. The pentamers are stabilized by disulfide bonds, as well as by interactions between the VP1 carboxy-terminus, which invades a neighboring pentamer (black curved lines). VP1 also binds to the underlying internal hydrophobic proteins VP2 and VP3. (B) To infect cells, SV40 interacts with the glycolipid receptor ganglioside GM1 on the plasma membrane, internalizes, and traffics to the endolysosomes (step 1). The virus then targets to the endoplasmic reticulum (ER) using a lipid-sorting mechanism (step 2), from where it crosses the ER membrane to access the cytosol (step 3). Upon entering the cytosol, SV40 mobilizes into the nucleus (step 4), where ensuing transcription and replication of the viral genome causes lytic infection or cellular transformation. NPC: nuclear pore complex.

Mentions: In this review, we will discuss host entry of the PyV simian virus 40 (SV40) due to the wealth of available information; where relevant, other PyVs will also be described. SV40 is the archetype PyV, displaying both genetic and structural similarity to human PyVs. Structurally, SV40 contains a circular doubled-stranded DNA genome of approximately five kilobases that encodes seven genes, three structural genes called VP1, VP2, VP3, and four non-structural genes called VP4, large T antigen, small T antigen, and agno protein [3,5,9,11]. As a non-enveloped virus, SV40 lacks a surrounding envelope and instead contains a protein capsid composed of 360 VP1 copies arranged as 72 pentamers that are displayed on the viral surface (Figure 1A). The pentamers are stabilized by disulfide bonds, as well as by interactions between the VP1 carboxy-terminus, which invades a neighboring pentamer [12,13]. VP1 also associates with the underlying internal hydrophobic proteins VP2 and VP3, which along with VP1, bind to the genome [14]. When fully assembled, SV40 is approximately 45–50 nm in diameter [5,9,12].


How Polyomaviruses Exploit the ERAD Machinery to Cause Infection
Simian virus 40 (SV40) structure and entry pathway. (A) SV40 consists of 360 VP1 copies arranged as 72 pentamers, which are localized on the viral surface. The pentamers are stabilized by disulfide bonds, as well as by interactions between the VP1 carboxy-terminus, which invades a neighboring pentamer (black curved lines). VP1 also binds to the underlying internal hydrophobic proteins VP2 and VP3. (B) To infect cells, SV40 interacts with the glycolipid receptor ganglioside GM1 on the plasma membrane, internalizes, and traffics to the endolysosomes (step 1). The virus then targets to the endoplasmic reticulum (ER) using a lipid-sorting mechanism (step 2), from where it crosses the ER membrane to access the cytosol (step 3). Upon entering the cytosol, SV40 mobilizes into the nucleus (step 4), where ensuing transcription and replication of the viral genome causes lytic infection or cellular transformation. NPC: nuclear pore complex.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC5035956&req=5

viruses-08-00242-f001: Simian virus 40 (SV40) structure and entry pathway. (A) SV40 consists of 360 VP1 copies arranged as 72 pentamers, which are localized on the viral surface. The pentamers are stabilized by disulfide bonds, as well as by interactions between the VP1 carboxy-terminus, which invades a neighboring pentamer (black curved lines). VP1 also binds to the underlying internal hydrophobic proteins VP2 and VP3. (B) To infect cells, SV40 interacts with the glycolipid receptor ganglioside GM1 on the plasma membrane, internalizes, and traffics to the endolysosomes (step 1). The virus then targets to the endoplasmic reticulum (ER) using a lipid-sorting mechanism (step 2), from where it crosses the ER membrane to access the cytosol (step 3). Upon entering the cytosol, SV40 mobilizes into the nucleus (step 4), where ensuing transcription and replication of the viral genome causes lytic infection or cellular transformation. NPC: nuclear pore complex.
Mentions: In this review, we will discuss host entry of the PyV simian virus 40 (SV40) due to the wealth of available information; where relevant, other PyVs will also be described. SV40 is the archetype PyV, displaying both genetic and structural similarity to human PyVs. Structurally, SV40 contains a circular doubled-stranded DNA genome of approximately five kilobases that encodes seven genes, three structural genes called VP1, VP2, VP3, and four non-structural genes called VP4, large T antigen, small T antigen, and agno protein [3,5,9,11]. As a non-enveloped virus, SV40 lacks a surrounding envelope and instead contains a protein capsid composed of 360 VP1 copies arranged as 72 pentamers that are displayed on the viral surface (Figure 1A). The pentamers are stabilized by disulfide bonds, as well as by interactions between the VP1 carboxy-terminus, which invades a neighboring pentamer [12,13]. VP1 also associates with the underlying internal hydrophobic proteins VP2 and VP3, which along with VP1, bind to the genome [14]. When fully assembled, SV40 is approximately 45–50 nm in diameter [5,9,12].

View Article: PubMed Central - PubMed

ABSTRACT

To infect cells, polyomavirus (PyV) traffics from the cell surface to the endoplasmic reticulum (ER) where it hijacks elements of the ER-associated degradation (ERAD) machinery to penetrate the ER membrane and reach the cytosol. From the cytosol, the virus transports to the nucleus, enabling transcription and replication of the viral genome that leads to lytic infection or cellular transformation. How PyV exploits the ERAD machinery to cross the ER membrane and access the cytosol, a decisive infection step, remains enigmatic. However, recent studies have slowly unraveled many aspects of this process. These emerging insights should advance our efforts to develop more effective therapies against PyV-induced human diseases.

No MeSH data available.


Related in: MedlinePlus