May 17, 2017
Hypothesis: Virus families use receptor families.
Abstract: Based on the information available there is substantial evidence that virus families use receptor families.
Introduction: In 1982 Yale researchers led by Dr. Lentz began to suspect that the rabies virus bound acetylcholine receptors. Within a few years they had proven their suspicions and created the conceptual idea that the reason viruses do not infect all cell types was that viruses entered cells using different receptors like keys to doorknobs. Subsequent research matching viruses to receptors reveals the possibility that virus families use receptor families. The following paper will be a review of 3 virus families and the possible receptor families associated with them.
Analysis of Hypothesis:
Three viral families have substantial evidence connecting them to specific receptor families: Polyomaviruses, Herpes viruses, and Flaviviruses. The polyomaviruses BK and JC along with herpes virus HHV8 have direct evidence of binding to specific receptors. The Herpes viruses and flaviviruses have indirect but highly suggestive evidence of association with receptors that will be discussed.
Polyomaviruses may bind ganglioside receptors. The Bk virus has been found to bind ganglioside receptors. The JC virus has been found to bind serotonin receptors. Serotonin receptors had at one time been classified as a ganglioside receptor. Transgenic mice forced to express the SV40 virus have adaptively over expressed serotonin receptors. It is highly likely that this SV40 and other polyomaviruses also bind these ganglioside/serotonin receptors.
Herpes viruses may bind estrogen receptors. The HHV8, a gamma-herpes like EBV, has specifically been found to bind the alpha estrogen receptor. The other types of herpes viruses may bind the other estrogen receptors. Although binding has not been proven HHV1 a gamma-herpes has been found to be estrogen receptor dependent during infection. Also consider that the beta estrogen receptors cycle to the mitochondria which is where the alpha-herpes viruses like Herpes Zoster has been found. The EBV and CMV are found in the nucleus like the HHV8 which suggests that they use either the alpha estrogen receptors or the estrogen-related-receptors (like progesterone). Do gamma-herpes use alpha receptors, alpha-herpes use beta-estrogen receptors, and beta-herpes use estrogen-related receptors?
Considering reactivation: The gamma-herpes HHV1 and HHV2 have been found to reactivate with estrogen which seems to support this notion. The beta-herpes CMV has been found to reactivate with estradiol. Estradiol increases the expression of both progesterone and estrogen receptors.
The Flaviviruses may bind the melanocortin receptors. Addition of melanin had a protective effect against the semliki forest virus and the west nile virus slowing the infection rate. The flavivirus Hepatitis C which can infect for years has the same diseases associated with it as the genetic Griscelli syndrome like neutropenia, thrombocytopenia, and NK cell dysfunction. Griscelli syndrome is the result of melanosomes, melanin pigment containing vesicles, failing to move. MCR1 stimulates melanosomes and could be one of the receptors Hepatitis C uses.
What is even more suggestive is if you consider where the other melanocortin receptors exist and where the other flaviviruses are found. MCR5 is on B cells which during dengue infections appears disrupted and could explain why second exposures to the virus are so harsh. MCR2 otherwise known as the ACTH receptor normally binds ACTH the first hormone involved in an embryo's brain growing and we have a flavivirus, ZIKA, which seems to stunt the growth of baby's brains. Yellow fever and hepatitis C infect the liver which has MCR4. West nile infects the kidney which may mean it primarily uses MCR3. These associations are suggestive and need to be considered.
The hypothesis " Virus families use receptor families" is suggestive but more data needs to be collected to validate these receptor-virus matches. Furthermore this hypothesis should be applied to other virus families such as flu viruses with dopamine receptors, enteroviruses with acetylcholine receptors, reoviruses with beta-adrenergic receptors, human papillomaviruses with cannabinoid receptors, and retroviruses with the albumin binding receptors like the luteinizing hormone receptor.
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