Herpes simplex 2, along with HIV-1, cause life-long infections that effects only humans. It has the capability of becoming latent by infecting the trigeminal ganglia and dorsal root ganglia.

Their lytic replication cycle begins by binding to the host cell. This is completed by using four out of seven surface glycoprotein (gB, gD, gH, and gL). Attachment of HSV-2 to the host cell is accomplished through gB and/or gC to its respective receptor, heparin sulfate proteoglycans (HSPG). Entry is completed by fusing the virus’ membrane to that of the host cell through the interactions between gD and its receptor. gD will then undergo a conformational change that forms the gH/ gL complex. This activation will trigger gB to bring the virus and the cell closer together, ultimately fusing the two membranes.

Once the HSV-2 materials are released into the cytoplasm, the capsid holding the viral genome will travel to the nucleus. The capsid will dock itself to NPCs (Nuclear Pore Complexes) and the viral DNA will be injected inside the nucleus. Studies have shown that viral proteins VP1 and VP2 associate with nucleoporins Nup358 and Nup214 to have favorable binding of the capsid and nucleus.

The next step is the expression and replication of HSV-2. Integratation of the HSV genome into that of its host is essential. The virus undergoes sequential transcription of viral transcription factors. The viral genome is then circularized in the nucleus for replication to proceed using the host’s polymerase. These will be copied and produce concatemers, which consists of multiple copies of the viral genome in a linear form. The mRNA is then translocated to the cytoplasm to translate the protein. A unique feature of HSV is the assembly of the capsid inside of the actual nucleus; usually the capsid is formed in the cytoplasm and translocated into the nucleus. Herpes simplex virus’ capsid mostly consist of VP5, along with lesser players such as VP19C, VP23, and VP26. It also involves the HSV-encoded proteases and scaffolding protein, pre-VP22a. Once the HSV capsids are assembled and the viral genome is inside, the internal components of the capsid will undergo maturation and leave the nucleus. 

For the Herpes Simplex Virus-2 to acutaly leave the host cell, it requires nuclear egress complex (NEC) consisted of type-II viral membrane U_L34 protein & U_L31.