A new look at the immunopathogenesis of infection caused by the human immunodeficiency virus

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Abstract

Thanks to the achievements of biotechnology and genetics, numerous features of reproduction of the human immunodeficiency virus and its immunopathogenesis have been established. Genetic studies have called into question the African origin of the virus. Thus, the number of individuals with mutational changes in the CCR5∆32 allele among the population providing genetic protection against human immunodeficiency virus is decreasing from north to south. The probability of adaptation of the great ape virus in the human population is characterized. New biological effects and their influence on the immunopathogenesis of infection of the well-known human immunodeficiency virus genes Gag (structural proteins), Pol (enzymes) and Env (envelope glycoproteins), the proteins encoded by them, as well as a number of additional proteins have been discovered. Thus, the main task of the Tat gene is to stimulate the transcription of proviral deoxyribonucleic acid and the transport of ribonucleic acid from the nucleus to the cytoplasm of the cell. Rev promotes the synthesis of viral structural proteins and enzymes, ensures the availability of full-sized genomic ribonucleic acid for inclusion in the reproduced viral progeny. Viruses with the absence of the vif gene are about 1000 times less virulent compared to wild strains. The APOBEC3G factor inhibits the reproduction of lentiviruses in primates, but in humans it is characterized by polymorphism of biological effects. Viral protein R affects the rate of reproduction of the virus in T-lymphocytes, contributes to their destruction. It also promotes proteasomal degradation and protein modification. Vpr targets may be a structurally specific endonuclease subunit SLX4, uracil-deoxynucleoacid glycosylase 2, and a helicase-like transcription factor. Vpu is a powerful inhibitor of teterin by type 1 immunodeficiency viruses of group M, and in group N viruses it shows low activity. Vpu, Nef, and Env proteins of most lentiviruses are characterized by higher tropicity to the CD4 receptor compared to teterin, serine incorporation proteins. These proteins are incorporated into viral particles and reduce their infectivity by inhibiting fusion with target cells. The protein containing the tripartite motif 5a, the protein of mixovirus activity 2/B constitute an ancient system of protection against retroviruses and are extremely variable in their effectiveness to disrupt the reproduction of viruses.

About the authors

Alexander V. Moskalev

Kirov Military Medical Academy

Author for correspondence.
Email: alexmav195223@yandex.ru
ORCID iD: 0000-0002-3403-3850
SPIN-code: 8227-2647
Scopus Author ID: 58223117100

MD, Dr. Sci. (Med.), Professor

Russian Federation, Saint Petersburg

Boris Yu. Gumilevsky

Kirov Military Medical Academy

Email: gumbu@mail.ru
ORCID iD: 0000-0001-8755-2219
SPIN-code: 3428-7704
Scopus Author ID: 6602391269
ResearcherId: J-1841-2017

MD, Dr. Sci. (Med.), Professor

Russian Federation, Saint Petersburg

Vasiliy Ya. Apchel

Kirov Military Medical Academy; Herzen State Pedagogical University of Russia

Email: apchelvya@mail.ru
ORCID iD: 0000-0001-7658-4856
SPIN-code: 4978-0785
Scopus Author ID: 6507529350
ResearcherId: Е-8190-2019

MD, Dr. Sci. (Med.), Professor

Russian Federation, Saint Petersburg; Saint Petersburg

Vasiliy N. Cygan

Kirov Military Medical Academy

Email: vn-t@mail.ru
ORCID iD: 0000-0003-1199-0911
SPIN-code: 7215-6206
Scopus Author ID: 6603136317

MD, Dr. Sci. (Med.), Professor

 

   

 

Russian Federation, Saint Petersburg

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Supplementary files

Supplementary Files
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1. JATS XML
2. Fig. 1. Evolution of primate lentiviruses (on J. Flint, V. Racaniello, G. Rall et al. Principles of Virology. Fifth edition. Vol. II. 2020): a — zoonotic transmission of primate lentiviruses from lower primates to higher primates; b — phylogenetic tree showing the supposed evolutionary relationships between primate lentiviruses. Human viruses are indicated in red. Subspecies of chimpanzees: gsn — great spotted-nosed monkey; mus — mustachioed monkey; mon — Mona monkey; gor — gorilla; rcm — mangabey; cpz — chimpanzee; mnd — mandrill monkey; agm — African green monkey; mac — makaka; lhoest — obez'yana L,Khoesta (gornaya obez'yana); sun — solnechnokhvostaya obez'yana; syk — obez'yana Sayksa; col — obez'yana kolobus

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3. Fig. 2. Mechanisms of Tat and F function in the HIV-1 reproduction cycle (on J. Flint, V. Racaniello, G. Rall et al. Principles of Virology. Fifth edition. Vol. II. 2020)

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4. Fig. 3. Adaptive functions of auxiliary proteins of the human immunodeficiency virus 1 (on J. Flint, V. Racaniello, G. Rall et al. Principles of Virology. Fifth edition. Vol. II. 2020): the main targets of the human immunodeficiency virus 1 (red); auxiliary proteins of the human immunodeficiency virus 1 (green). Their location in an infected cell and the main stages of the human immunodeficiency virus 1 reproductive cycle are shown. Lentiviral helper proteins block the restriction proteins of the host in whose body the virus multiplies, but not their counterparts, even related species. This has been demonstrated in the development of animal models for HIV-1

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5. Fig. 4. Mechanism of action of APOBEC3G and degradation by Vif (on J. Flint, V. Racaniello, G. Rall et al. Principles of Virology. Fifth edition. Vol. II. 2020)

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