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7.1.2 Virion Structure

As a typical herpesviral particle, KSHV consists of three major morphologically

distinct parts: a highly ordered nucleocapsid encasing a linear double-strand viral

DNA, an outer envelope bilayer containing large amounts of viral glycoprotein on

the surface, and an electron-dense layer called the tegument layer between the cap-

sid and the outer envelope (Table 7.1).

The three-dimensional (3D) structure of the KSHV capsid was analyzed in

detail using cryo-electron microscopy reconstruction. Similar to the structure of

herpes simplex virus type 1 (HSV-1) and human cytomegalovirus (HCMV), the

KSHV capsid possesses a shell composed of 12 pentons, 150 hexons, and 320 tri-

plexes arranged on a T = 16 icosahedral lattice [ 9 ]. Four viral structural proteins

constitute these units. The major capsid protein (MCP) encoded by open reading

frame (ORF) 25 forms hexameric and pentameric capsomers; the triplexes are het-

erotrimeric structures encoded by one molecule of ORF62 and two molecules of

ORF26 [ 10 ]. These proteins show significant amino acid sequence homology to the

capsid proteins of alpha- and betaherpesviruses. ORF65, as the smallest and highly

antigenic capsid protein, is attached to the upper domain of the major capsid pro-

tein in hexons but not to that in pentons [ 11 ]. ORF56 also plays a pivotal in the

KSHV capsid assembly process [ 12 , 13 ]. There are at least three capsid species: A

(empty capsid), B (containing structural protein), and C (containing the viral

genome) [ 10 ]. B-capsids contain various inner scaffolding proteins that probably

Table 7.1 Major KSHV virion structural proteins

Category Gene Function

Capsid proteins ORF17.5 Scaffold protein

ORF25 Major capsid protein

ORF26 Capsid triplex homologs

ORF62 Capsid triplex homologs

ORF65 Capsid-associated structural protein

Envelope proteins ORF8 gB

K8.1 Glycoprotein

ORF22 gH

ORF39 gM

ORF47 gL

ORF53 gN

ORF68 Glycoprotein

Tegument proteins ORF21 TK

ORF33 Tegumentation and viral assembly

ORF45 Assembled capsid-tegument complexes transportation

ORF52 Tegumentation and viral assembly

ORF63 Tegument protein

ORF64 Scaffold protein interact with capsid and tegument protein

ORF75 Viral particle transportation

7 KSHV Epidemiology and Molecular Biology