Now that some background information has been established for Herpes Simplex Virus-2, one of the questions that you might be wondering is: “When did humans first get introduced to HSV-2?”. To answer that, I would have to go WAAAYYY back to the evolution of humans.
HSV-1, which causes cold sores, has been associated with even our earliest ancestors when they split from the chimpanzees, which is not the case for HSV-2. Interestingly, HSV-2 could have been avoided by humans had it not been due to an intermediate hominin species that allowed the virus to re-infect our ancestors. Herpes Simplex Virus-2 was a virus that preyed on African apes; when the precursor human officially split off from chimpanzees they did not take the HSV-2 with them (only HSV-1). It was all thanks to the intermediate hominin species, Parathropus boisei, that HSV-2 got reintroduced to the human species.1
Scientists hypothesize that HSV-2 may have initially competed with HSV-1 in the mouth of hominins, until it adapted a new environment in the genitals. A virologist from Cambridge University, Dr. Charlotte Houldcroft, stated that HSV-2 would have had to undergo a certain genetic mutation with a combination of copious fluid exchange for the virus to overcome the species barrier and ultimately infect hominins through consumption or intercourse. Once Herpes Simplex Virus-2 invaded Homo erectus, it persisted due to its easily transferrable nature. If you ever happen to get genital herpes and you want someone to blame, you can thank Parathropus boisei; a picture can be found below!
Reference: (1) https://www.sciencedaily.com/releases/2017/10/171001225317.htm
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 UL34 protein & UL31.
Herpes simplex virus 2 (HSV-2), which is one of the two types of HSV, is most known for being associated with genital herpes. Yikes! The structure is spherical and consists of double-stranded DNA, which is encased by an isosapentahedral capsid. The said capsid is then enclosed in a tightly-associated tegument. These layers are then further enclosed in a lipid bilayer envelope. The figure below should help with the envisionment of the actual HSV-2 structure. In terms of the virus’ size, it can get pretty big. The actual virion, which includes the DNA, the capsid, the tegument, and the lipid bilayer membrane, can have a range from 120 nm to 300 nm. The capsid itself is constructed by 162 capsomers arranged in an icosapentahedral shape. As for proteins found in the lipid bilayer, glycoproteins are one of the compounds that the membrane consists of. Their presence allows certain viruses to obtain various unique properties, as well as antigens for the host to be able to respond to. Like many viruses, HSV-2 cannot physically move independently; it is subject to movement by environmental interactions. I hope this post gave you a good overview of the fascinating structure of Herpes Simplex 2!
I have decided to dedicate this post to Herpes Simplex 2 Virus!
I met this microbe at the CDC Museum on a Friday with some of my classmates. We decided to do our site visit there since we have never seen it, and I honestly wanted to try on the HazMat suit.
It was actually not very easy to find the actual entrance to the museum since our Uber ride dropped us off 5 minutes away and the security guards kept pointing us in the wrong direction. When we finally made it up to the entrance, we were greeted by a friendly security guard and a lady at the front office. They kindly informed us on which exhibits to check out to help us with our school assignment.
As my friends and I were looking around the exhibits, I noticed a lot of recognizable microbes such as Ebola and HIV. It was cool, but I wanted to choose something that I was unfamiliar with to make the assignment more exciting. That is when I met Herpes simplex virus 2, the microbe that stole the spotlight! This microbe was displayed using fluorescent antibodies so it, along with other microbes, was depicted in bright neon colors. After doing some research, I have determined that Herpes simplex virus 2 is from the simplexvirus genus. I can not wait to update you guys on this very cool virus on my next blog post.
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