Next Article in Journal
Comparison Study of Different Extracts of Plectranthus madagascariensis, P. neochilus and the Rare P. porcatus (Lamiaceae): Chemical Characterization, Antioxidant, Antimicrobial and Cytotoxic Activities
Previous Article in Journal
Assessment of DNA Topoisomerase I Unwinding Activity, Radical Scavenging Capacity, and Inhibition of Breast Cancer Cell Viability of N-alkyl-acridones and N,N′-dialkyl-9,9′-biacridylidenes
Article Menu
Issue 5 (May) cover image

Export Article

Open AccessReview

HIV Vaccine Mystery and Viral Shell Disorder

Goh’s BioComputing, Singapore 548957, Singapore
Center for Computational Biology, Indiana and Bioinformatics, Indiana University School of Medicine, Indianapolis, IN 46202, USA
Department of Biological Sciences, University of Idaho, Moscow, ID 83844, USA
Institute for Bioinformatics and Evolutionary Studies, University of Idaho, Moscow, ID 83844, USA
Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA
Institute for Biological Instrumentation, Russian Academy of Sciences, Moscow Region, Pushchino 142290, Russia
Author to whom correspondence should be addressed.
Biomolecules 2019, 9(5), 178;
Received: 27 February 2019 / Revised: 25 April 2019 / Accepted: 30 April 2019 / Published: 8 May 2019
(This article belongs to the Special Issue HIV: ART and Immune Activation)
PDF [21619 KB, uploaded 8 May 2019]


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. View Full-Text
Keywords: HIV; intrinsic disorder; unstructured; immune escape; glycoconjugate; smallpox; polio; rabies; yellow fever; herpes; hepatitis HIV; intrinsic disorder; unstructured; immune escape; glycoconjugate; smallpox; polio; rabies; yellow fever; herpes; hepatitis

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Share & Cite This Article

MDPI and ACS Style

Goh, G. .-M.; Dunker, A.K.; Foster, J.A.; Uversky, V.N. HIV Vaccine Mystery and Viral Shell Disorder. Biomolecules 2019, 9, 178.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics



[Return to top]
Biomolecules EISSN 2218-273X Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top