Ultrastructure and Assembly of Human Herpesvirus6 HHV6

Z. Hong Zhoua, James K. Stoopsa, Gerhard R.F. Kruegera,b aDepartment of Pathology and Laboratory Medicine, University of Texas Health Science Center at Houston Medical School, Houston, TX 77030, USA bDepartment of Anatomy II, The University of Cologne, Cologne 50924, Germany

Introduction

Human herpesvirus-6 (HHV-6) is a ubiquitous member of the betaherpesvirus subfamily of the Herpesviridae family. The HHV-6 genome is arranged colinearly and codes for approximately 67% of proteins in common with human cytomegalovirus (HCMV), and 21% with all other herpesviruses. Sequence comparison shows that it is closely related to HHV-7 and HCMV.

HHV-6 is a lymphotropic herpesvirus infecting up to 90%of the population and establishing latent or persistent infections for a lifetime (Salahuddin et al., 1986; Josephs et al., 1988; Levine et al., 1992; Krueger et al., 1998a). Clinical features of HHV-6 infection are described in Part II of this book.

There are two variants of HHV-6, HHV-6A and HHV-6B with obvious gen-omic polymorphism within a variant (Ablashi et al., 1991, 1993; Schirmer et al., 1991). Both also vary in their tissue distribution in human and in their tissue culture cells for propagation (Lusso et al., 1988; Black et al., 1989; Ablashi et al., 1991; Di Luca et al., 1994). Some virologists recently regard HHV-6A and HHV-6B as separate herpesviruses (see Chapters 1 and 6 in this book). All ultrastructural features described in the following are derived from HHV-6A grown in HSB2 cells.

Despite variations in host range, genome size, and composition, HHV-6 shares common virion structures with other herpesviruses (Kramarsky and Sander, 1992) showing four basic elements: the core, the capsid, the tegument, and the envelope (Fig. 1). The core of the mature virion consists of double-stranded DNA (dsDNA) closely packed in a spherical capsid (Zhou et al., 1999). The capsid is a rigid icosahedral protein shell, 1200-1300 A in diameter, that encloses and protects the dsDNA core. The tegument is a poorly defined, asymmetric layer of host and viral proteins between the capsid and the envelope. It varies in thickness and distribution around the capsid with some of its proteins in close proximity and anchored to the capsid. The envelope is a host-derived lipid bilayer containing spikes of viral glycoproteins. The entire virion varies in diameter from 1400 to 3000 A, depending on the thickness of the tegument and the integrity of the envelope.

The eight known human herpesviruses are classified into three subfamilies (alpha-, beta- and gammaherpesviruses) based on shared biological properties (Table 1) (Roizman and Pellett, 2001). Alphaherpesviruses have a variable host range, short reproductive cycle, and rapid spread in culture. They establish latent infection primarily in neurons. This subfamily includes the human pathogens herpes simplex virus types 1 and 2 (HSV-1 and -2 or HHV-1 and -2) and varicella-Zoster virus (VZV or HHV-3). Betaherpesviruses have a more restricted host range, longer reproductive cycle, and slower growth in culture. The virus can remain latent in salivary glands, neurons, lymphocytes, and possibly other tissues. HCMV (i.e. HHV-5) and human herpesvirus types 6 and 7 (HHV-6, HHV-7) are members of this subfamily. Gammaherpesviruses include Epstein-Barr virus (EBV or HHV-4) and Kaposi's sarcoma-associated herpesvirus (KSHV) or HHV-8, both associated with certain lymphomas and other cancers. HHV-8 appears to have a more

Fig. 1 Basic architecture of the herpesvirus virion. The ds DNA genome is coiled in the protein capsid. The capsid is surrounded by various tegument proteins, some of which are anchored to the capsid, while others are free-floating. The envelope is a host-derived lipid bilayer containing spikes of viral glyco-protein. (Adapted from Kramarsky and Sander (1992) with permission from the publisher).

Ultrastructure Herpesvirus

Fig. 1 Basic architecture of the herpesvirus virion. The ds DNA genome is coiled in the protein capsid. The capsid is surrounded by various tegument proteins, some of which are anchored to the capsid, while others are free-floating. The envelope is a host-derived lipid bilayer containing spikes of viral glyco-protein. (Adapted from Kramarsky and Sander (1992) with permission from the publisher).

Table 1

The known human herpesviruses

Table 1

The known human herpesviruses

Virus

Subfamily

Genome length (kb)

Preferred host cells

Selective-associated diseases3

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