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The A, B, Cs of herpesvirus capsids.

Tandon R, Mocarski ES, Conway JF - Viruses (2015)

Bottom Line: Assembly of herpesvirus nucleocapsids shares significant similarities with the assembly of tailed dsDNA bacteriophages; however, important differences exist.Interaction of specific capsid forms with viral tegument proteins has been proposed to be a mechanism for quality control at the point of nuclear egress of mature particles.Here, we will review the available literature on these capsid forms and present data to debate whether A- and B-capsids play an important or an extraneous role in the herpesvirus life cycle.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology and Immunology, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216, USA. rtandon@umc.edu.

ABSTRACT
Assembly of herpesvirus nucleocapsids shares significant similarities with the assembly of tailed dsDNA bacteriophages; however, important differences exist. A unique feature of herpesviruses is the presence of different mature capsid forms in the host cell nucleus during infection. These capsid forms, referred to as A-, B-, and C-capsids, represent empty capsids, scaffold containing capsids and viral DNA containing capsids, respectively. The C-capsids are the closest in form to those encapsidated into mature virions and are considered precursors to infectious virus. The evidence supporting A- and B-capsids as either abortive forms or assembly intermediates has been lacking. Interaction of specific capsid forms with viral tegument proteins has been proposed to be a mechanism for quality control at the point of nuclear egress of mature particles. Here, we will review the available literature on these capsid forms and present data to debate whether A- and B-capsids play an important or an extraneous role in the herpesvirus life cycle.

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Transmission electron micrograph of a negatively stained preparation of purified extracellular HCMV (Towne) virions. The virion in the center is labeled for the genomic DNA (D), Capsid (C), Tegument (T), and envelope (E) layers. The dense bodies, composed of tegument proteins but no nucleocapsid, can be seen to the left of the labeled virion. Scale 40 nm.
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viruses-07-00899-f001: Transmission electron micrograph of a negatively stained preparation of purified extracellular HCMV (Towne) virions. The virion in the center is labeled for the genomic DNA (D), Capsid (C), Tegument (T), and envelope (E) layers. The dense bodies, composed of tegument proteins but no nucleocapsid, can be seen to the left of the labeled virion. Scale 40 nm.

Mentions: Examination of mature cytoplasmic or extracellular HCMV virions reveals four distinct layers: viral DNA (D), capsid (C), tegument (T), and envelope (E), which can all be distinguished in transmission electron micrographs of negatively stained samples (Figure 1). During productive HCMV infection, capsids are visible by electron microscopy as early as two days post infection in the nucleus of infected cells. Three populations of capsids can be identified: empty A-capsids, scaffold containing B-capsids and viral genomic DNA containing C-capsids (Figure 2C). These capsid populations are unevenly distributed in the nucleoplasm. Typically, B-capsids make up the majority (~80%), followed by C-capsids (15%) and then A-capsids (5%) [17]. Most capsid forms are found to be tightly associated with the darker stained areas of the nucleus, termed nuclear inclusions (NI), which are nuclear replication compartments (NRC) that contain replicating virus DNA [18] (Figure 2C). These capsids do not accumulate in the vicinity of nuclear envelope suggesting a rather rapid transport of capsids from the NRC to the inner nuclear membrane (INM) for nuclear egress. The presence of NI is a characteristic of cells infected by any herpesvirus although cytoplasmic inclusions (CI) appear to be unique to cytomegalovirus infected cells (Figure 2) [18,37,38,39,40]. While NI are associated with the centers of viral DNA replication in the nucleus, CI are associated with virus maturation events occurring in the cytoplasm [41,42,43,44]. Also, the changes in the size and morphology of the nucleus that are observed in HCMV infected cells are distinct from the changes in cells infected with other herpesviruses [11]. Capsids are assembled in the nucleus from viral proteins that are imported from the cytoplasm and the assembly can take place in the absence of viral DNA as evidenced by HSV capsid formation in a virus-free and in an in vitro cell free system [45,46]. In HCMV, capsids assemble from major capsid protein (MCP/pUL86), triplex monomer (TRI1/pUL46, also called minor capsid binding protein (mcBP)), triplex dimer (TRI2/pUL85, also called minor capsid protein (mCP)) and smallest capsid protein (SCP/pUL48A) with help from a pUL80-based scaffold that translocates MCP into the nucleus and organizes the capsid shell before being cleaved by the viral maturational protease (pUL80a) [17,18]. Preformed capsids process the scaffold as viral DNA is encapsidated by the TER complex (UL89, UL56, UL51) through a PORT (UL104) [18]. A putative capsid vertex specific complex (CVSC) constituted of pUL77 and pUL93 is believed to bind onto nucleocapsid pentamers, with pUL95, pUL52, pUL32, and pUL96 added later on for nucleocapsid stabilization [18]. Staining for major capsid protein (MCP) in infected cells demonstrates accumulation of this protein in NI but not anywhere else in the nucleus [40,47]. It is not clear how capsid proteins and capsids themselves are restricted to the NI in the absence of a physical barrier. The A-, B-, and C-capsids are stable enough to be readily isolated from the nuclei of HSV-1-infected cells [25]. For HCMV, although all three types of capsids can be harvested, the C-capsids lose their stability very quickly after harvest (personal experience and [48]).


The A, B, Cs of herpesvirus capsids.

Tandon R, Mocarski ES, Conway JF - Viruses (2015)

Transmission electron micrograph of a negatively stained preparation of purified extracellular HCMV (Towne) virions. The virion in the center is labeled for the genomic DNA (D), Capsid (C), Tegument (T), and envelope (E) layers. The dense bodies, composed of tegument proteins but no nucleocapsid, can be seen to the left of the labeled virion. Scale 40 nm.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4379554&req=5

viruses-07-00899-f001: Transmission electron micrograph of a negatively stained preparation of purified extracellular HCMV (Towne) virions. The virion in the center is labeled for the genomic DNA (D), Capsid (C), Tegument (T), and envelope (E) layers. The dense bodies, composed of tegument proteins but no nucleocapsid, can be seen to the left of the labeled virion. Scale 40 nm.
Mentions: Examination of mature cytoplasmic or extracellular HCMV virions reveals four distinct layers: viral DNA (D), capsid (C), tegument (T), and envelope (E), which can all be distinguished in transmission electron micrographs of negatively stained samples (Figure 1). During productive HCMV infection, capsids are visible by electron microscopy as early as two days post infection in the nucleus of infected cells. Three populations of capsids can be identified: empty A-capsids, scaffold containing B-capsids and viral genomic DNA containing C-capsids (Figure 2C). These capsid populations are unevenly distributed in the nucleoplasm. Typically, B-capsids make up the majority (~80%), followed by C-capsids (15%) and then A-capsids (5%) [17]. Most capsid forms are found to be tightly associated with the darker stained areas of the nucleus, termed nuclear inclusions (NI), which are nuclear replication compartments (NRC) that contain replicating virus DNA [18] (Figure 2C). These capsids do not accumulate in the vicinity of nuclear envelope suggesting a rather rapid transport of capsids from the NRC to the inner nuclear membrane (INM) for nuclear egress. The presence of NI is a characteristic of cells infected by any herpesvirus although cytoplasmic inclusions (CI) appear to be unique to cytomegalovirus infected cells (Figure 2) [18,37,38,39,40]. While NI are associated with the centers of viral DNA replication in the nucleus, CI are associated with virus maturation events occurring in the cytoplasm [41,42,43,44]. Also, the changes in the size and morphology of the nucleus that are observed in HCMV infected cells are distinct from the changes in cells infected with other herpesviruses [11]. Capsids are assembled in the nucleus from viral proteins that are imported from the cytoplasm and the assembly can take place in the absence of viral DNA as evidenced by HSV capsid formation in a virus-free and in an in vitro cell free system [45,46]. In HCMV, capsids assemble from major capsid protein (MCP/pUL86), triplex monomer (TRI1/pUL46, also called minor capsid binding protein (mcBP)), triplex dimer (TRI2/pUL85, also called minor capsid protein (mCP)) and smallest capsid protein (SCP/pUL48A) with help from a pUL80-based scaffold that translocates MCP into the nucleus and organizes the capsid shell before being cleaved by the viral maturational protease (pUL80a) [17,18]. Preformed capsids process the scaffold as viral DNA is encapsidated by the TER complex (UL89, UL56, UL51) through a PORT (UL104) [18]. A putative capsid vertex specific complex (CVSC) constituted of pUL77 and pUL93 is believed to bind onto nucleocapsid pentamers, with pUL95, pUL52, pUL32, and pUL96 added later on for nucleocapsid stabilization [18]. Staining for major capsid protein (MCP) in infected cells demonstrates accumulation of this protein in NI but not anywhere else in the nucleus [40,47]. It is not clear how capsid proteins and capsids themselves are restricted to the NI in the absence of a physical barrier. The A-, B-, and C-capsids are stable enough to be readily isolated from the nuclei of HSV-1-infected cells [25]. For HCMV, although all three types of capsids can be harvested, the C-capsids lose their stability very quickly after harvest (personal experience and [48]).

Bottom Line: Assembly of herpesvirus nucleocapsids shares significant similarities with the assembly of tailed dsDNA bacteriophages; however, important differences exist.Interaction of specific capsid forms with viral tegument proteins has been proposed to be a mechanism for quality control at the point of nuclear egress of mature particles.Here, we will review the available literature on these capsid forms and present data to debate whether A- and B-capsids play an important or an extraneous role in the herpesvirus life cycle.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology and Immunology, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216, USA. rtandon@umc.edu.

ABSTRACT
Assembly of herpesvirus nucleocapsids shares significant similarities with the assembly of tailed dsDNA bacteriophages; however, important differences exist. A unique feature of herpesviruses is the presence of different mature capsid forms in the host cell nucleus during infection. These capsid forms, referred to as A-, B-, and C-capsids, represent empty capsids, scaffold containing capsids and viral DNA containing capsids, respectively. The C-capsids are the closest in form to those encapsidated into mature virions and are considered precursors to infectious virus. The evidence supporting A- and B-capsids as either abortive forms or assembly intermediates has been lacking. Interaction of specific capsid forms with viral tegument proteins has been proposed to be a mechanism for quality control at the point of nuclear egress of mature particles. Here, we will review the available literature on these capsid forms and present data to debate whether A- and B-capsids play an important or an extraneous role in the herpesvirus life cycle.

Show MeSH
Related in: MedlinePlus