94
represent different intermediates rather than a structurally homogenous group dur-
ing the process of KSHV capsid assembly and maturation [ 14 ]. Cryo-electron
tomography revealed that an internally localized, umbilicated portal complex exists
in the KSHV capsid [ 15 ].
Seven viral glycoproteins are interspersed in the envelope, including ORF8 (gB),ORF22 (gH), ORF39 (gM), ORF47 (gL), ORF53 (gN), K8.1, and ORF68 [ 16 – 21 ].
These glycoproteins function in mediating KSHV interactions with cell surface
receptors and virion entry into host cells. The tegument layer remains largely unde-
fined and is thought to be an amorphous structure. Several possible tegument pro-
teins have been characterized as tegument components based on the following
criteria: (1) resistance to protease digestion in the absence of detergent and (2) sus-
ceptibility to protease digestion with envelope dissolved [ 21 – 23 ]. Under these con-
ditions, ORF11, ORF21, ORF33, ORF45, ORF50, ORF52, ORF63, ORF64, and
ORF75 are considered tegument proteins with more to be characterized in the future
[ 21 – 23 ]. Studies on the structure of tegument in HSV-1 [ 24 , 25 ], HCMV [ 26 ], and
MHV-68 [ 27 ] suggest a two-layered organization of the tegument. The inner layer
may interact with the capsid, and the outer layer is loosely organized to conform to
the shape of the envelope [ 23 ]. A recent study of the KSHV virion showed that five
tegument densities cap each penton vertex. Each KSHV tegument density includes
a penton-binding globular region, a helix-bundle stalk region, and a β-sheet-rich
triplex-binding region [ 28 ]. The role of tegument proteins in mediating the interac-
tion of inner capsid and outer envelope suggests their function of tegumentation and
viral assembly and egress processes. Major KSHV virion structural proteins are
listed in Table 7.1.
7.1.3 Viral Genome
The KSHV genome is a double-stranded DNA consisting of a 140.5-kb-long unique
coding region flanked by a GC-rich terminal repeat region. About 90 ORFs are pres-
ent in this long unique region, including 66 Herpesvirus saimiri-conserved ORFs
[ 29 , 30 ]. The repeat regions are 803 bp in length and are 85% G+C. The number of
repeats varies at each end, but the total number remains at 35–45 [ 31 ].
Similar to other rhadinoviruses, KSHV has a large number of regulatory geneswith similarity to known cellular genes. This is probably due to the virus pirating
these genes from the host cell genome during evolution. They include IL-6, BCL-2,
several different interferon regulatory factor homologs, cyclin D, and other genes
whose function resembles that of their cellular homologs [ 32 ]. In addition, KSHV
has a significant number of unique genes that are not found in other herpesviruses.
These specific genes are named K1-K15 based on the locations from left to right in
the genome [ 33 ]. In addition, several noncoding RNAs, such as polyadenylated
nuclear RNA (PAN RNA), and 13 pre-miRNAs, encoding 25 mature microRNAs
(miRNAs), are encoded by KSHV [ 34 – 37 ].
S. Li et al.