HIV Vaccine Mystery and Viral Shell Disorder

Gerard Kian Meng Goh, A. Dunker, James A. Foster, Vladimir N. Uversky

Research output: Contribution to journalReview article

Abstract

Hundreds of billions of dollars have been spent for over three decades in the search for an effective human immunodeficiency virus (HIV) vaccine with no success. There are also at least two other sexually transmitted viruses, for which no vaccine is available, the herpes simplex virus (HSV) and the hepatitis C virus (HCV). Traditional textbook explanatory paradigm of rapid mutation of retroviruses cannot adequately address the unavailability of vaccine for many sexually transmissible viruses, since HSV and HCV are DNA and non-retroviral RNA viruses, respectively, whereas effective vaccine for the horsefly-transmitted retroviral cousin of HIV, equine infectious anemia virus (EIAV), was found in 1973. We reported earlier the highly disordered nature of proteins in outer shells of the HIV, HCV, and HSV. Such levels of disorder are completely absent among the classical viruses, such as smallpox, rabies, yellow fever, and polio viruses, for which efficient vaccines were discovered. This review analyzes the physiology and shell disorder of the various related and non-related viruses to argue that EIAV and the classical viruses need harder shells to survive during harsher conditions of non-sexual transmissions, thus making them vulnerable to antibody detection and neutralization. In contrast, the outer shell of the HIV-1 (with its preferential sexual transmission) is highly disordered, thereby allowing large scale motions of its surface glycoproteins and making it difficult for antibodies to bind to them. The theoretical underpinning of this concept is retrospectively traced to a classical 1920s experiment by the legendary scientist, Oswald Avery. This concept of viral shapeshifting has implications for improved treatment of cancer and infections via immune evasion.

Original languageEnglish (US)
JournalBiomolecules
Volume9
Issue number5
DOIs
StatePublished - May 8 2019

Fingerprint

Viral Vaccines
Viruses
Vaccines
HIV
Simplexvirus
Equine infectious anemia virus
Hepacivirus
Yellow fever virus
Immune Evasion
Smallpox
Textbooks
Rabies
Antibodies
RNA Viruses
Membrane Glycoproteins
Poliomyelitis
Retroviridae
HIV-1
Mutation
DNA

Keywords

  • glycoconjugate
  • hepatitis
  • herpes
  • HIV
  • immune escape
  • intrinsic disorder
  • polio
  • rabies
  • smallpox
  • unstructured
  • yellow fever

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

Cite this

HIV Vaccine Mystery and Viral Shell Disorder. / Goh, Gerard Kian Meng; Dunker, A.; Foster, James A.; Uversky, Vladimir N.

In: Biomolecules, Vol. 9, No. 5, 08.05.2019.

Research output: Contribution to journalReview article

Goh, Gerard Kian Meng ; Dunker, A. ; Foster, James A. ; Uversky, Vladimir N. / HIV Vaccine Mystery and Viral Shell Disorder. In: Biomolecules. 2019 ; Vol. 9, No. 5.
@article{f03c660614bf442b88b1984d741b7a26,
title = "HIV Vaccine Mystery and Viral Shell Disorder",
abstract = "Hundreds of billions of dollars have been spent for over three decades in the search for an effective human immunodeficiency virus (HIV) vaccine with no success. There are also at least two other sexually transmitted viruses, for which no vaccine is available, the herpes simplex virus (HSV) and the hepatitis C virus (HCV). Traditional textbook explanatory paradigm of rapid mutation of retroviruses cannot adequately address the unavailability of vaccine for many sexually transmissible viruses, since HSV and HCV are DNA and non-retroviral RNA viruses, respectively, whereas effective vaccine for the horsefly-transmitted retroviral cousin of HIV, equine infectious anemia virus (EIAV), was found in 1973. We reported earlier the highly disordered nature of proteins in outer shells of the HIV, HCV, and HSV. Such levels of disorder are completely absent among the classical viruses, such as smallpox, rabies, yellow fever, and polio viruses, for which efficient vaccines were discovered. This review analyzes the physiology and shell disorder of the various related and non-related viruses to argue that EIAV and the classical viruses need harder shells to survive during harsher conditions of non-sexual transmissions, thus making them vulnerable to antibody detection and neutralization. In contrast, the outer shell of the HIV-1 (with its preferential sexual transmission) is highly disordered, thereby allowing large scale motions of its surface glycoproteins and making it difficult for antibodies to bind to them. The theoretical underpinning of this concept is retrospectively traced to a classical 1920s experiment by the legendary scientist, Oswald Avery. This concept of viral shapeshifting has implications for improved treatment of cancer and infections via immune evasion.",
keywords = "glycoconjugate, hepatitis, herpes, HIV, immune escape, intrinsic disorder, polio, rabies, smallpox, unstructured, yellow fever",
author = "Goh, {Gerard Kian Meng} and A. Dunker and Foster, {James A.} and Uversky, {Vladimir N.}",
year = "2019",
month = "5",
day = "8",
doi = "10.3390/biom9050178",
language = "English (US)",
volume = "9",
journal = "Biomolecules",
issn = "2218-273X",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "5",

}

TY - JOUR

T1 - HIV Vaccine Mystery and Viral Shell Disorder

AU - Goh, Gerard Kian Meng

AU - Dunker, A.

AU - Foster, James A.

AU - Uversky, Vladimir N.

PY - 2019/5/8

Y1 - 2019/5/8

N2 - Hundreds of billions of dollars have been spent for over three decades in the search for an effective human immunodeficiency virus (HIV) vaccine with no success. There are also at least two other sexually transmitted viruses, for which no vaccine is available, the herpes simplex virus (HSV) and the hepatitis C virus (HCV). Traditional textbook explanatory paradigm of rapid mutation of retroviruses cannot adequately address the unavailability of vaccine for many sexually transmissible viruses, since HSV and HCV are DNA and non-retroviral RNA viruses, respectively, whereas effective vaccine for the horsefly-transmitted retroviral cousin of HIV, equine infectious anemia virus (EIAV), was found in 1973. We reported earlier the highly disordered nature of proteins in outer shells of the HIV, HCV, and HSV. Such levels of disorder are completely absent among the classical viruses, such as smallpox, rabies, yellow fever, and polio viruses, for which efficient vaccines were discovered. This review analyzes the physiology and shell disorder of the various related and non-related viruses to argue that EIAV and the classical viruses need harder shells to survive during harsher conditions of non-sexual transmissions, thus making them vulnerable to antibody detection and neutralization. In contrast, the outer shell of the HIV-1 (with its preferential sexual transmission) is highly disordered, thereby allowing large scale motions of its surface glycoproteins and making it difficult for antibodies to bind to them. The theoretical underpinning of this concept is retrospectively traced to a classical 1920s experiment by the legendary scientist, Oswald Avery. This concept of viral shapeshifting has implications for improved treatment of cancer and infections via immune evasion.

AB - Hundreds of billions of dollars have been spent for over three decades in the search for an effective human immunodeficiency virus (HIV) vaccine with no success. There are also at least two other sexually transmitted viruses, for which no vaccine is available, the herpes simplex virus (HSV) and the hepatitis C virus (HCV). Traditional textbook explanatory paradigm of rapid mutation of retroviruses cannot adequately address the unavailability of vaccine for many sexually transmissible viruses, since HSV and HCV are DNA and non-retroviral RNA viruses, respectively, whereas effective vaccine for the horsefly-transmitted retroviral cousin of HIV, equine infectious anemia virus (EIAV), was found in 1973. We reported earlier the highly disordered nature of proteins in outer shells of the HIV, HCV, and HSV. Such levels of disorder are completely absent among the classical viruses, such as smallpox, rabies, yellow fever, and polio viruses, for which efficient vaccines were discovered. This review analyzes the physiology and shell disorder of the various related and non-related viruses to argue that EIAV and the classical viruses need harder shells to survive during harsher conditions of non-sexual transmissions, thus making them vulnerable to antibody detection and neutralization. In contrast, the outer shell of the HIV-1 (with its preferential sexual transmission) is highly disordered, thereby allowing large scale motions of its surface glycoproteins and making it difficult for antibodies to bind to them. The theoretical underpinning of this concept is retrospectively traced to a classical 1920s experiment by the legendary scientist, Oswald Avery. This concept of viral shapeshifting has implications for improved treatment of cancer and infections via immune evasion.

KW - glycoconjugate

KW - hepatitis

KW - herpes

KW - HIV

KW - immune escape

KW - intrinsic disorder

KW - polio

KW - rabies

KW - smallpox

KW - unstructured

KW - yellow fever

UR - http://www.scopus.com/inward/record.url?scp=85065888886&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85065888886&partnerID=8YFLogxK

U2 - 10.3390/biom9050178

DO - 10.3390/biom9050178

M3 - Review article

VL - 9

JO - Biomolecules

JF - Biomolecules

SN - 2218-273X

IS - 5

ER -