102
polymerase, and the replicated genomes are evenly distributed to the daughter cells.
Latency is the default pathway of KSHV infection, and although no infectious viri-
ons are produced during this stage, it retains the potential for virion production [ 22 ,
100 ]. It is commonly accepted that ORF73/LANA, ORF72/v-cyclin, ORF71/vFLIP,
and the K12/kaposin family of proteins (kaposin A, B and C) are latent genes, as are
the 13 pre-miRNAs that can yield approximately 25 miRNAs [ 101 , 102 ].
ORF73/LANA, a major KSHV-encoded latent protein, is located in the nucleusof latently infected cells and has been detected in PEL and KS tumor cells in vivo,
in B cells in MCD, and in every latent cell type infected in vitro [ 101 , 103 , 104 ].
LANA is a multifunctional protein consisting of 1,162 amino acids, and it is approx-
imately 220–230 kDa in size. LANA has three major domains. The C-terminal
domain binds directly to the conserved TR sequences of the KSHV genome, the
N-terminal domain docks onto the host chromosome to hitch a ride during host
mitosis to maintain a stable copy number in the latently infected cells, and the cen-
tral region includes highly acidic amino acid repeats. One of the most critical func-
tions of LANA is maintaining efficient segregation of the viral genomes as a circular
Fig. 7.1 Diagram demonstrating the sequence of events in the processes of KSHV entry and intra-
cellular trafficking. ( 1 ) KSHV utilizes macropinocytosis and clathrin-mediated endocytosis to
facilitate the rapid entry of viral particles into different cell types; ( 2 ) KSHV modulates the diverse
host cellular proteins for its trafficking from the cytoplasm to the nucleus; ( 3 ) KSHV induces the
cytoplasmic ERK1/2, NF-κB, and Nrf2 transcription factors very early during infection to initiate
viral gene expression soon after the entry of the viral genome into the nucleus
S. Li et al.