scholarly journals Macrophage Tropism in Pathogenic HIV-1 and SIV Infections

Viruses ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 1077
Author(s):  
Matthew Moeser ◽  
Joshua R. Nielsen ◽  
Sarah B. Joseph
Keyword(s):  
Macrophage Infection ◽  
Myeloid Lineage ◽  
Viral Loads ◽  
Disease States ◽  
Macrophage Tropism ◽  
Natural Hosts ◽  
Primary Driver ◽  
Primate Lentiviruses ◽  
Post Entry ◽  
Hiv 1

Most myeloid lineage cells express the receptor and coreceptors that make them susceptible to infection by primate lentiviruses (SIVs and HIVs). However, macrophages are the only myeloid lineage cell commonly infected by SIVs and/or HIVs. The frequency of infected macrophages varies greatly across specific host and virus combinations as well as disease states, with infection rates being greatest in pathogenic SIV infections of non-natural hosts (i.e., Asian nonhuman primates (Asian NHPs)) and late in untreated HIV-1 infection. In contrast, macrophages from natural SIV hosts (i.e., African NHPs) are largely resistant to infection due to entry and/or post-entry restriction mechanisms. These highly variable rates of macrophage infection may stem from differences in the host immune environment, entry and post-entry restriction mechanisms, the ability of a virus to adapt to efficiently infect macrophages, and the pleiotropic effects of macrophage-tropism including the ability to infect cells lacking CD4 and increased neutralization sensitivity. Questions remain about the relationship between rates of macrophage infection and viral pathogenesis, with some evidence suggesting that elevated levels of macrophage infection may contribute to greater pathogenesis in non-natural SIV hosts. Alternatively, extensive infection of macrophages may only emerge in the context of high viral loads and immunodeficiency, making it a symptom of highly pathogenic infections, not a primary driver of pathogenesis.

Accumulated Mutations Cause Significant Fitness Losses and are Associated with Decreased Viral Loads During Early HIV-1 Infection

2019 ◽  
Author(s):  
Chu Wang ◽  
Donglai Liu ◽  
Tao Zuo ◽  
Bhavna Hora ◽  
Fangping Cai ◽  
...  
Keyword(s):  
Viral Loads ◽  
Hiv 1

scholarly journals Foamy Viruses, Bet, and APOBEC3 Restriction

Viruses ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 504
Author(s):  
Ananda Ayyappan Jaguva Vasudevan ◽  
Daniel Becker ◽  
Tom Luedde ◽  
Holger Gohlke ◽  
Carsten Münk
Keyword(s):  
Current Knowledge ◽  
Regulatory Protein ◽  
Host Population ◽  
Life Cycles ◽  
Restriction Factors ◽  
Host Restriction ◽  
Open Questions ◽  
Foamy Viruses ◽  
Natural Hosts ◽  
Hiv 1

Non-human primates (NHP) are an important source of viruses that can spillover to humans and, after adaptation, spread through the host population. Whereas HIV-1 and HTLV-1 emerged as retroviral pathogens in humans, a unique class of retroviruses called foamy viruses (FV) with zoonotic potential are occasionally detected in bushmeat hunters or zookeepers. Various FVs are endemic in numerous mammalian natural hosts, such as primates, felines, bovines, and equines, and other animals, but not in humans. They are apathogenic, and significant differences exist between the viral life cycles of FV and other retroviruses. Importantly, FVs replicate in the presence of many well-defined retroviral restriction factors such as TRIM5α, BST2 (Tetherin), MX2, and APOBEC3 (A3). While the interaction of A3s with HIV-1 is well studied, the escape mechanisms of FVs from restriction by A3 is much less explored. Here we review the current knowledge of FV biology, host restriction factors, and FV–host interactions with an emphasis on the consequences of FV regulatory protein Bet binding to A3s and outline crucial open questions for future studies.

scholarly journals Nationwide Study of Drug Resistance Mutations in HIV-1 Infected Individuals under Antiretroviral Therapy in Brazil

2021 ◽  
Vol 22 (10) ◽  
pp. 5304
Author(s):  
Ana Santos-Pereira ◽  
Vera Triunfante ◽  
Pedro M. M. Araújo ◽  
Joana Martins ◽  
Helena Soares ◽  
...  
Keyword(s):  
Drug Resistance ◽  
People Living With Hiv ◽  
Resistance Mutations ◽  
Subtype C ◽  
Viral Loads ◽  
Drug Resistance Mutations ◽  
Subtype B ◽  
Low Prevalence ◽  
Living With Hiv ◽  
Hiv 1

The success of antiretroviral treatment (ART) is threatened by the emergence of drug resistance mutations (DRM). Since Brazil presents the largest number of people living with HIV (PLWH) in South America we aimed at understanding the dynamics of DRM in this country. We analyzed a total of 20,226 HIV-1 sequences collected from PLWH undergoing ART between 2008–2017. Results show a mild decline of DRM over the years but an increase of the K65R reverse transcriptase mutation from 2.23% to 12.11%. This increase gradually occurred following alterations in the ART regimens replacing zidovudine (AZT) with tenofovir (TDF). PLWH harboring the K65R had significantly higher viral loads than those without this mutation (p < 0.001). Among the two most prevalent HIV-1 subtypes (B and C) there was a significant (p < 0.001) association of K65R with subtype C (11.26%) when compared with subtype B (9.27%). Nonetheless, evidence for K65R transmission in Brazil was found both for C and B subtypes. Additionally, artificial neural network-based immunoinformatic predictions suggest that K65R could enhance viral recognition by HLA-B27 that has relatively low prevalence in the Brazilian population. Overall, the results suggest that tenofovir-based regimens need to be carefully monitored particularly in settings with subtype C and specific HLA profiles.

CD4+ T cell count, HIV-1 viral loads and demographic variables of newly identified patients with HIV infection in Wuhan, China

2013 ◽  
Vol 85 (10) ◽  
pp. 1687-1691 ◽  
Author(s):  
Man-Qing Liu ◽  
Li Tang ◽  
Wen-Hua Kong ◽  
Ze-Rong Zhu ◽  
Jin-Song Peng ◽  
...  
Keyword(s):  
T Cell ◽  
Hiv Infection ◽  
Cell Count ◽  
Demographic Variables ◽  
Cd4 T Cell ◽  
Viral Loads ◽  
Hiv 1 ◽  
Cd4 T Cell Count

HIV-1 gp120 and chemokine activation of Pyk2 and mitogen-activated protein kinases in primary macrophages mediated by calcium-dependent, pertussis toxin–insensitive chemokine receptor signaling

Blood ◽  
2001 ◽  
Vol 98 (10) ◽  
pp. 2909-2916 ◽  
Author(s):  
Manuela Del Corno ◽  
Qing-Hua Liu ◽  
Dominique Schols ◽  
Erik de Clercq ◽  
Sandra Gessani ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Pertussis Toxin ◽  
Chemokine Receptor ◽  
Calcium Release ◽  
Mitogen Activated Protein Kinase ◽  
Macrophage Infection ◽  
Amino Terminal ◽  
Crac Channels ◽  
Mitogen Activated Protein ◽  
Hiv 1

Abstract Human immunodeficiency virus type 1 (HIV-1) uses the chemokine receptors CCR5 and CXCR4 as coreceptors for entry. It was recently demonstrated that HIV-1 glycoprotein 120 (gp120) elevated calcium and activated several ionic signaling responses in primary human macrophages, which are important targets for HIV-1 in vivo. This study shows that chemokine receptor engagement by both CCR5-dependent (R5) and CXCR4-dependent (X4) gp120 led to rapid phosphorylation of the focal adhesion-related tyrosine kinase Pyk2 in macrophages. Pyk2 phosphorylation was also induced by macrophage inflammatory protein-1β (MIP-1β) and stromal cell–derived factor-1α, chemokine ligands for CCR5 and CXCR4. Activation was blocked by EGTA and by a potent blocker of calcium release–activated Ca++(CRAC) channels, but was insensitive to pertussis toxin (PTX), implicating CRAC-mediated extracellular Ca++ influx but not Gαi protein-dependent mechanisms. Coreceptor engagement by gp120 and chemokines also activated 2 members of the mitogen-activated protein kinase (MAPK) superfamily, c-Jun amino-terminal kinase/stress-activated protein kinase and p38 MAPK. Furthermore, gp120-stimulated macrophages secreted the chemokines monocyte chemotactic protein-1 and MIP-1β in a manner that was dependent on MAPK activation. Thus, the gp120 signaling cascade in macrophages includes coreceptor binding, PTX-insensitive signal transduction, ionic signaling including Ca++ influx, and activation of Pyk2 and MAPK pathways, and leads to secretion of inflammatory mediators. HIV-1 Env signaling through these pathways may contribute to dysregulation of uninfected macrophage functions, new target cell recruitment, or modulation of macrophage infection.

scholarly journals Utility of HIV-1 DNA genotype in determining antiretroviral resistance in patients with low or undetectable HIV RNA viral loads

2018 ◽  
Vol 73 (11) ◽  
pp. 3129-3136 ◽  
Author(s):  
Narjis Boukli ◽  
Anders Boyd ◽  
Marianne Collot ◽  
Jean-Luc Meynard ◽  
Pierre-Marie Girard ◽  
...  
Keyword(s):  
Viral Loads ◽  
Hiv Rna ◽  
Antiretroviral Resistance ◽  
Hiv 1

scholarly journals Anti-CD45RO Suppresses Human Immunodeficiency Virus Type 1 Replication in Microglia: Role of Hck Tyrosine Kinase and Implications for AIDS Dementia

2006 ◽  
Vol 80 (1) ◽  
pp. 62-72 ◽  
Author(s):  
Mee-Ohk Kim ◽  
Hyeon-Sook Suh ◽  
Qiusheng Si ◽  
Bruce I. Terman ◽  
Sunhee C. Lee
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Myeloid Lineage ◽  
Aids Dementia ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Macrophages and microglia are productively infected by HIV-1 and play a pivotal role in the pathogenesis of AIDS dementia. Although macrophages and microglia express CD45, a transmembrane protein tyrosine phosphatase, whether modulation of its activity affects human immunodeficiency virus type 1 (HIV-1) replication is unknown. Here, we report that of the five human CD45 isoforms, microglia express CD45RB and CD45RO (RB > RO) and treatment of microglia with a CD45 agonist antibody αCD45RO (UCHL-1) inhibits HIV-1 replication. αCD45RO prevented HIV-1 negative factor (Nef)-induced autophosphorylation of hematopoietic cell kinase (Hck), a myeloid lineage-specific Src kinase. Recombinant CD45 protein also inhibited HIV-1-induced Hck phosphorylation in microglia. Antennapedia-mediated delivery of Hck Src homology domain 3 (SH3), a domain that binds to the Nef PxxP motif with high affinity, reduced HIV-1-induced Hck phosphorylation and HIV-1 production in microglia. HIV-1-induced LTR transactivation was observed in U38 cells stably overexpressing wild-type Hck but not kinase-inactive Hck. In microglia, αCD45RO reduced activation of transcription factors (NF-κB and CCAAT enhancer binding protein) necessary for LTR transactivation in macrophages. These results establish that in myeloid lineage cells, Nef interacts with the Hck SH3 domain, resulting in autophosphorylation of Hck and an increase in HIV-1 transcription. αCD45RO-mediated inhibition of HIV-1 replication in microglia identifies the CD45 protein tyrosine phosphatase as a potential therapeutic target for HIV-1 infection/AIDS dementia.

Efficacy of Nevirapine-Based HAART in HIV-1-Infected, Treatment-Naive Persons with High and Low Baseline Viral Loads

2001 ◽  
Vol 2 (4) ◽  
pp. 317-322 ◽  
Author(s):  
François Raffi ◽  
Véronique Reliquet ◽  
Daniel Podzamczer ◽  
Richard Pollard
Keyword(s):  
Viral Loads ◽  
Treatment Naïve ◽  
Hiv 1

scholarly journals The characteristics of the HIV-1 Env glycoprotein contribute to viral pathogenesis

2021 ◽  
Author(s):  
Silvia Perez-Yanes ◽  
Maria Pernas ◽  
Silvia Marfil ◽  
Romina Cabrera-Rodríguez ◽  
Raquel Ortiz ◽  
...  
Keyword(s):  
Functional Characteristic ◽  
Elite Controllers ◽  
Clinical Progression ◽  
Viral Control ◽  
Clinical Phenotypes ◽  
Viral Loads ◽  
Variable Contribution ◽  
Gp120 Subunit ◽  
Hiv 1

The understanding of HIV-1 pathogenesis and clinical progression is incomplete because of the variable contribution of host, immune and viral factors. The involvement of viral factors has been investigated in extreme clinical phenotypes from rapid progressors to long-term non-progressors (LTNPs). Among HIV-1 proteins, the envelope glycoprotein complex (Env) has concentrated many studies for its important role in the immune response and in the first steps of viral replication. In this study, we analyzed the contribution of 41 Envs from 24 patients with different clinical progression rates and viral loads (VLs), LTNP-Elite Controllers (LTNP-ECs); Viremic LTNPs (vLTNPs), and non-controller’s individuals contemporary to LTNPs or recent, named Old and Modern progressors. We analyzed the Env expression, the fusion and cell-to-cell transfer capacities as well as viral infectivity. The sequence and phylogenetic analysis of Envs were also performed. In every functional characteristic, the Envs from subjects with viral control (LTNP-ECs and vLTNPs) showed significant lower performance compared to those from the progressor individuals (Old and Modern). Regarding sequence analysis, the variable loops of the gp120 subunit of the Env (i.e., V2, V4 and mainly V5) of the progressor individuals showed longer and more glycosylated sequences than controller subjects. Therefore, HIV-1 Envs presenting poor viral functions and shorter sequences were associated with viremic control and the non-progressor clinical phenotype, whereas functional Envs were associated with the lack of virological control and progressor clinical phenotypes. These correlations support the central role of Env genotypic and phenotypic characteristics in the in vivo HIV-1 infection and pathogenesis.

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