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Non-traumatic neurological conditions in medico-legal work
Published in Helen Whitwell, Christopher Milroy, Daniel du Plessis, Forensic Neuropathology, 2021
HIV infection is widespread throughout the world and remains a major clinical problem. In forensic practice, it is important to remember that a proportion of the intravenous drug abuser (IVDA) population are HIV positive. HIV infection results in the progressive depletion of CD4 T lymphocytes and subsequent immunosuppression causing acquired immune deficiency syndrome (AIDS). Neuropathology is seen in 70–90 per cent of AIDS cases, although much of this is caused by opportunistic infections (Morgello 2018). HIV itself can cause nervous system pathology, with neuropathology directly attributable to HIV being seen in 20–30 per cent of cases (Navia et al. 1986). HIV encephalopathy (HIVE) is a white matter disease characterised by multinucleated giant cells. HIVE has been shown to be more prevalent in IVDAs than in homosexuals. The HIV-related protein gp41 can be demonstrated immunohistochemically in relation to many multinucleated giant cells. Macroscopically, the HIVE brain often appears normal; microscopically, there are foci of perivascular lymphocytes and microglial nodules often lying adjacent to multinucleated giant cells. Vacuolar myelopathy is seen in AIDS patients and resembles subacute combined degeneration of the cord. The degeneration develops in the posterior and lateral columns of the spinal cord, and there is axonal degeneration. In AIDS patients, the disorder is not associated with vitamin B12 deficiency.
Neuropathogenesis of viral infections
Published in Avindra Nath, Joseph R. Berger, Clinical Neurovirology, 2020
Avindra Nath, Joseph R. Berger
There are several mechanisms by which viral proteins may become available to the extracellular environment: (a) When a cell ruptures, all its contents including all structural and non-structural viral proteins become available to the extracellular environment. (b) There may be a restricted expression of viral genes whereby some proteins are over expressed but a non-replicative state of the viral genome is maintained [62] (e.g., in HIV infected astrocytes regulatory genes tat, nef and rev are over expressed). Furthermore, during the normal course of viral replication, not all structural proteins formed within infected cells get incorporated into the viral structure. These proteins are either degraded by the cells or are available for extracellular release. Viral proteins, such as Tat protein of HIV, may be actively secreted by the cell [63,64]. (c) All viral particles formed by infected cells are not replication competent, thus structural proteins of the virus in the form of defective viral particles may have access to and affect uninfected cells [65]. In fact, for animal and plant viruses, most viral particles produced are defective/non-infectious. (d) The viral coat protein may be shed upon viral entry [66]. (e) Viral proteins may interact with surrounding uninfected cells by cell-to-cell contact with an infected cell. For example, gp41 is a transmembrane protein of HIV that is expressed on the surface of infected cells, which may induce neuronal injury to cells in close proximity [67].
HIV-1: Biology
Published in Niel T. Constantine, Johnny D. Callahan, Douglas M. Watts, Retroviral Testing, 2020
Niel T. Constantine, Johnny D. Callahan, Douglas M. Watts
The gp41 antigen spans the inner and outer membrane of the virus, and thus is often referred to as the transmembrane glycoprotein antigen. This particular antigen contains important variable regions, and therefore may be specific for each type or strain of the HIV-1 virus. The gpl20 antigen is the major component of the external envelope and is responsible for the 72 knobs or spikes of the envelope. Significant variability in gpl20 (as high as 15%) between the HIVs occurs in the hypervariable regions of the molecule; this may be responsible for the inability of the immune system to contain the virus. Together, the gp41 and gpl20 antigens are involved with the fusion and attachment of HIV to the CD4 molecule on the host cells. The identification of antibodies to the envelope antigens is extremely important for the laboratory diagnosis of HIV infection. Antibody to at least one env component must be detected in the host in order to confirm infection (Chapter 4).
Antimicrobial peptides and other peptide-like therapeutics as promising candidates to combat SARS-CoV-2
Published in Expert Review of Anti-infective Therapy, 2021
Masoumeh Sadat Mousavi Maleki, Mosayeb Rostamian, Hamid Madanchi
The entry of HIV-1 virus is remarkably similar to the entry of SARS-CoV2 virus into their target cells [89,90]. HIV-1 virus enters the host cell with two glycoprotein subunits on its surface, namely the gp120 subunit (equivalent to S1 of SARS-CoV-2) which is responsible for binding to the receptor, and the gp41 subunit (equivalent to S2 of SARS-CoV-2) which is responsible for fusion to the host cell membrane. Refolding of the N-terminal heptad repeat (NHR) and the C-terminal heptad repeat (CHR) of the gp41 subunit in the form of a 6 helixes bundle (6-HB), brings the virus and the cell membranes closer together, leading to a fusion reaction. NHR and CHR sequence-derived antiviral peptides, such as the FDA-approved drug T20 or Enfuvirtide, can competitively inhibit the formation of viral 6-HB, thereby inhibiting the fusion of the virus to the host cell membranes and ultimately inhibiting the virus entry [22,91]. Because HIV-1 gp41 protein is structurally and functionally similar to SARS-CoV2 protein S2, the question is whether Enfuvirtide can inhibit SARS-CoV2 entry into the cell as well. In an in silico study using molecular docking and molecular dynamic (MD), Calligari et al. suggest Enfuvirtide as a SARS-Cov2 inhibitor [92]. More researches on this FDA-approved drug and conducting clinical trials in this area could help develop drug discovery and treatment for COVID-19.
The current and future role of nanovaccines in HIV-1 vaccine development
Published in Expert Review of Vaccines, 2021
Christopher P. Karch, Gary R. Matyas
Much of the focus of the development of nanovaccines for inducing antibodies against HIV-1 has focused on NAbs [81]. Attempts have been made to make a VLP from the HIV-1 virus itself and, while capable of inducing Tier-2 NAbs, these types of vaccines have many of the same problems as the whole HIV-1 virus, including low-levels of Env presentation, unstable and incomplete Env spikes, and further than ideal distances between the spikes [82,83]. Other attempts have been made to generate fusion VLPs, fusing HIV-1 Gag or capsid proteins from other viruses with HIV-1 proteins such as gp160, gp120, trimeric gp140, V3 loop, V1V2 loop, and the CD4 binding site, resulted in mixed findings with only some capable of inducing NAbs in animal models [84–94]. When focusing on responses specifically to gp41, animals immunized with a Gag-VLP presenting MPER did not induce high titers of NAbs. However, presentation of gp41 itself on non-eVLPs from other viruses resulted in some neutralization in animal models [95,96].
Gold nanoparticles for preparation of antibodies and vaccines against infectious diseases
Published in Expert Review of Vaccines, 2020
The V3β peptide of the HIV-1 gp120 protein in complex with 2-nm gold glyconanoparticles was used as an immunogen to prepare a prototype HIV vaccine [104]. Rabbits were immunized three times intramuscularly with 50 μg of the complex. The resulting antibodies had a high titer and neutralizing activity against HIV-1. The HIV-1 Gag p17 peptide conjugated to 2-nm gold glyconanoparticles increased the proliferation of HIV-specific CD4+ and CD8+ T cells and induced the secretion of the highly functional TNF-α and IL-1β cytokines, as compared to the unconjugated peptide [105]. Also, GNPs conjugated with the gp120 and gp41 viral proteins were used as a platform for the delivery of immunogens in the preparation of an HIV-1 vaccine [106].