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Introduction to Cells, DNA, and Viruses
Published in Patricia G. Melloy, Viruses and Society, 2023
So where do viruses fit into the idea of evolution? Well, viruses do undergo allelic changes (changes in the particular version of a gene) even in their small genome. These changes can happen quite rapidly given that viruses have a short generation time if they quickly enter the lytic phase of growth upon host entry, and they do not have the same proofreading mechanisms in many cases as eukaryotic cells (like our cells) do to protect the integrity of the genome. Therefore, random mutations occur as viruses replicate, and there is always the potential that an allele will give the virus an advantage over previous iterations, leading to a viral variant. Another source of variation is recombination or DNA rearrangements. Recombination can occur if two or more different virus strains infect a host cell at the same time. The viruses can exchange some genetic material through a process known as horizontal gene transfer, resulting in viruses with some genomic segments from the original parent virus and some segments from the other virus. Recombination events are common with different types of influenza A viruses (Lostroh 2019). We will return to this idea when we discuss the 1918 influenza pandemic. There actually is evidence from bacteriophage and simian immunodeficiency virus (SIV) that the virus and the host it infects can coevolve (Lostroh 2019).
Heterocyclic Drugs from Plants
Published in Rohit Dutt, Anil K. Sharma, Raj K. Keservani, Vandana Garg, Promising Drug Molecules of Natural Origin, 2020
Debasish Bandyopadhyay, Valeria Garcia, Felipe Gonzalez
Human immunodeficiency virus or HIV is a type of lentivirus. This virus debilitates a person’s immune system. The immune system is crippled through destruction of essential cells which fight the diseases and infections that constantly attempt to strike human body (HIV basics, 2018). Lentivirus, a genus of retroviruses that generate long-standing and fatal diseases characterized by long incubation periods, in the mammalians including human. The basis of HIV was discovered when scientists identified a specific chimpanzee species in Central Africa (About HIV/AIDS, 2018). The chimpanzee version of the immunodeficiency virus is called SIV. Scientists concluded that SIV was transmitted onto humans when they hunted the simians and contamination of blood took place. Thus SIV was transformed to HIV. This virus was originated in Africa, became more prominent until it escalated worldwide. Body fluids are the carriers of HIV transmission. Subsequent attack is targeted to the immune system, or more specifically the body’s CD4 cells (T cells). The CD4 cells are primarily responsible, alongside the immune system, to encounter the infections and other disease-containing entities (HIV.gov, 2017). When left untreated, HIV can destroy the CD4 cells, once again damaging body’s propensity of inhibiting infections. Once the body is attacked by HIV, it loses the inherent defense mechanism and over time body becomes unable to defend against infection and subsequent illness. HIV makes the body weak and open to be attacked by other microbes/parasites that weaken the health even more.
HIV and AIDS
Published in Rae-Ellen W. Kavey, Allison B. Kavey, Viral Pandemics, 2020
Rae-Ellen W. Kavey, Allison B. Kavey
Inevitably, identification of these cases led to investigation of the origin of the human immunodeficiency virus with a focus on central, sub-Saharan Africa where the earliest known cases were identified. As early as the mid-1980s, a monkey or simian virus that very closely resembled HIV-2 was discovered to cause immunodeficiency in captive macaques. Subsequently, this simian immunodeficiency virus (SIV) was found in multiple primates in sub-Saharan Africa with the prevalence of naturally occurring infection ranging widely; in most species, the virus appeared to cause no detectable illness. Ultimately, phylogenetic studies show that SIVsmm – for “SIV sooty mangabey” – was confirmed as the monkey ancestor for HIV-2 with transfer to humans by skin or mucous membrane contact with blood, presumably related to bushmeat hunting. A simian virus that closely resembled HIV-1 was discovered in chimpanzees in 1990 in south-east Cameroon. Using non-invasive analysis of urine and fecal samples, scientists discovered that in monkeys, SIVcpz (SIV chimpanzee) is spread primarily through sexual routes with animal migration carrying the infection from one community to another. Combined behavioral and virologic studies show that SIVcpz infection is associated with an AIDS-like illness in chimpanzee colonies. As with SIVsmm, spread of SIVcpz to humans is thought to have occurred via incidents related to hunting and slaughtering of chimpanzees as bushmeat.
HIV-1 cure strategies: why CRISPR?
Published in Expert Opinion on Biological Therapy, 2021
Andrew J. Atkins, Alexander G. Allen, Will Dampier, Elias K. Haddad, Michael R. Nonnemacher, Brian Wigdahl
There are two predominant animal models used to test HIV-1 cure strategies: the rhesus macaque (RM) model using simian immunodeficiency virus (SIV) and humanized mouse models using HIV-1. The RM model is supported by numerous reports and has been shown to recapitulate human disease [20,80,81]. Additionally, the RM latent reservoir is seeded rapidly following infection [82]. However, to date, there are no published reports of SIV-targeting CRISPR/Cas9 being tested in an RM model. However, the CRISPR/Cas9 system using the RM model would require testing CRISPR against SIV beginning with ex vivo experiments using RM CD4 + T cells. This is a viable strategy; SIV Gag can be detected by ELISA allowing efficient quantitation of CRISPR/Cas9 effectiveness in vitro. For these experiments, the SIVmac239 strain could be used. Furthermore, this experimental paradigm could also be applied to infected RM PBMCs suppressed into latency by ART. Following ex vivo experiments, the next step would be to establish proof of principle in vivo in the RM model. Notably, a limitation of the RM model in validating CRISPR/Cas9 strategies is imposed by the differences between SIV and HIV-1 sequences. The sequence specificity of CRISPR/Cas9 gRNAs would necessitate design of SIV-specific gRNAs for use in the RM model and in vivo assessment would be for SIV-specific targets not necessarily present in the HIV-1 genome.
Chronic obstructive pulmonary disease in HIV
Published in Expert Review of Respiratory Medicine, 2021
Katerina Byanova, Ken M. Kunisaki, Joshua Vasquez, Laurence Huang
Additional limitations to quantifying MΦ reservoirs of HIV include the detection of dysfunctional/noninfectious viral sequences and measurement of the virus from contaminating T-cells or phagocytic remnants [67,70]. Experiments conducted in nonhuman primates (NHP) infected with simian immunodeficiency virus (SIV) have overcome many of these limitations and largely support the idea of MΦ as a site of viral persistence in the lung. To evaluate the specific myeloid subsets infected with SIV, Kurodra et al. performed cellular labeling experiments in NHP and observed infection of short-lived MΦ subsets in the lung interstitium as well as longer-lived alveolar macrophages [72]. In other studies, confirmation that macrophage-associated SIV is functionally intact was achieved using modified quantitative viral outgrowth assays (QVOA) on MΦ collected from the BAL of infected animals [74,75]. Unfortunately, the progression of SIV in NHP does not accurately reflect the course of HIV in humans [76]. Therefore, prior studies, performed in humans or NHP, do not adequately address the role of local reservoirs in the progression of COPD during chronic-treated HIV and highlight the need for more comprehensive human-based studies to characterize tissue-reservoirs in the lung and determine the impact of HIV persistence on the progression of HIV-associated lung disease.
Combination therapies currently under investigation in phase I and phase II clinical trials for HIV-1
Published in Expert Opinion on Investigational Drugs, 2020
Hanh Thi Pham, Subin Yoo, Thibault Mesplède
Whereas key findings suggest that antibody- and cell-based approaches or the use of immune checkpoint inhibitors may help the host immune system to target the HIV reservoirs, a major weakness in the field is that very few trials are designed to test whether this targeting is sufficient to delay or impede viral rebound after treatment interruption. The ultimate goal in our field is to eliminate the need of daily ART to control viral replication (viral remission) or to remove all traces of infectious HIV from the body (viral eradication). In both cases, both cellular and anatomical localizations of the HIV reservoirs need to be further understood. In this regard, we believe that using simian immunodeficiency virus (SIV)-infected rhesus macaques as a source of cells and tissues is an important avenue of research that can help this characterization and the evaluation of curative interventions. So-called ‘last-gift’ whole body donation from people living with HIV represents a similarly outstanding opportunity to better understand the HIV reservoirs. However, the limited numbers of potential donors and the diverse nature of patients’ clinical histories are unlikely to allow for systematic studies. Thus, our inability to study the deep-tissue HIV reservoirs in people represents the single biggest challenge in attaining our objectives.