Human herpes simplex virus: Life cycle and development of inhibitors

Abstract

WHO reports that 90% of human population is infected by different types of herpesviruses, which develop latency or cause oral and genital herpes, conjunctivitis, eczema herpeticum, and other diseases. Herpesvirus almost always accompanies HIV-infection and complicates AIDS treatment. Herpes simplex virus type 1 is one of the most wide spread viruses from the Herpesviridae family. HSV virion, genome structure, replication mechanisms, antiherpes drug development strategies, including design of prodrugs, and mutations causing ACV-resistance in clinical HSV isolates are discussed in this review.

Molecular studies on HSV: Replication rate, infection capacity and progeny

“…(Spear, 2004, Salameh et al, 2012, Kukhanova et al, 2014. Despite structural disparities and different interactions with gD, the binding to one of the three receptors described above leads to the same endpoint: membrane fusion (Heldwein et al, 2008, Gianni et al, 2009, Kukhanova et al, 2014.…”

“…The genome comprises two covalently linked components, L (long) and S (short), with unique sequences UL (107.09 kbp) and US (12 kbp), respectively, flanked by large inverted repeats (Figure 1.3). The UL and US units of the genome can invert relative to one another, producing four different types of DNA molecules (Kukhanova et al, 2014). The genes of the long and short unique sequences are designated UL1 to UL56, and US1 to US12, respectively.…”

“…HSV glycoproteins have roles in attachment and entry into the host cell, even though the function of each glycoprotein varies according to the overall pathogenesis and immune evasion strategy of the virus (Kukhanova et al, 2014). Nevertheless, it is known that gB, gC, gD, gH and gL are essential for the infection process (Reske et al, 2007).…”

“…As members of the Herpesviridae family, they comprise four major components: (i) a core containing a linear double-stranded DNA (dsDNA) molecule (Pellet et al, 2003); (ii) an icosahedral capsid surrounding the core with 162 capsomers (Kukhanova et al, 2014); (iii) an amorphous structure asymmetrically distributed around the capsid designated tegument; and (iv) a host-derived lipid envelope with embedded viral glycoproteins on its surface (Kukhanova et al, 2014). Based on their biological properties, HSV can be further placed in the alphaherpesviridae subfamily due to their variable host range, short reproductive cycle, rapid spread in culture and ability to destroy infected cells (Wagner et al, 1997).…”

Immune- and Nonimmune-Compartment-Specific Interferon Responses Are Critical Determinants of Herpes Simplex Virus-Induced Generalized Infections and Acute Liver Failure

“…The importance of studying HSV-induced ALF is underscored by the immunocompromised populations it affects, mainly patients undergoing chemotherapy, bone marrow transplant recipients, HIV patients, and women in the third trimester of pregnancy (5,6). HSV-1 infects via the mucosae of the mouth, eyes, or genitalia, where it undergoes lytic replication in the epithelium (7). During infection of these mucosae, the virus infects innervating sensory neurons, traveling in a retrograde direction in the facial neurons back to mostly sensory ganglia, wherein HSV-1 establishes latency (8).…”