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Viruses
Special Issues
HTLV-HIV Coinfection
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HTLV-HIV Coinfection

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Human Virology and Viral Diseases".

Deadline for manuscript submissions: closed (31 July 2022) | Viewed by 14209

Special Issue Editors

Dr. Alejandro Vallejo

E-Mail Website
Guest Editor
Laboratory of Immunovirology, Infectious Diseases Department, Health Research Institute Ramon y Cajal (IRyCIS), Ramon y Cajal University Hospital, 28034 Madrid, Spain
Interests: HIV-1; HTLV-2; HCV; immunology; innate immunity; T and B cell responses; miRNAs; small extracellular vesicles
Dr. Maria Abad Fernandez

E-Mail Website
Guest Editor
UNC HIV Cure Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Interests: CD8 T cells; HIV-1

Special Issue Information

Dear Colleagues,

The human retroviruses HIV-1 and HTLV-1/HTLV-2 share similar routes of transmission but cause different diseases. The immune mediated mechanisms by which HTLVs can affect HIV-1 disease in co-infected hosts are the scope of this research topic that includes innate immune responses, T-cell and antibody responses, and their genetic control.

During co-infection with HIV-1, HTLV-2 modulates the cellular microenvironment inhibiting HIV-1 progression. This is achieved because it up-regulates viral suppressive chemokine expression, activates the JAK/STAT pathway, reduces the activation of T, B and NK cells, and modulates the host miRNA profiles, among others. These alterations have been mainly attributed to the effects of the HTLV-2 regulatory protein Tax and suggest that HTLV-2 exerts a protective role against HIV-1 infection.

The effect of HIV-1/HTLV-1 co-infection on immunological and pathological conditions is still controversial since some studies indicate a worsening of HIV-1 infection, while others do not show any clinically relevant effects in HIV-positive people.The differences between the two HIV-1/HTLV-1 and HIV-1/HTLV-2 co-infections are highlighted and further discussed in this Special Issue that will contain reviews and updates on recent advances in research focused on each of these areas.

Dr. Alejandro Vallejo
Dr. Maria Abad Fernandez
Guest Editors

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Keywords

  • human T cell leukemia virus
  • adult T cell leukemia
  • HTLV-associated myelopathy
  • HIV-1
  • HIV-2
  • HBZ/APH
  • tax
  • accessory proteins
  • new HTLV viruses
  • transcription control
  • cell cycle/senescence
  • genome instability
  • clinical trials
  • animal models
  • viral entry
  • epidemiology
  • pathogenesis
  • T cell cytotoxicity
  • B cell response – neutralyzing antibodies
  • innate response – NK cell activity

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Published Papers (5 papers)

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Editorial

Jump to: Research, Review

2 pages, 190 KiB  
Editorial
Concluding Remarks for Special Issue HTLV-HIV Co-Infections
by Alejandro Vallejo and María Abad-Fernández
Viruses 2023, 15(4), 963; https://doi.org/10.3390/v15040963 - 14 Apr 2023
Viewed by 1161
Abstract
During the early 1980s, the first 3 human retroviruses were identified: human T-lymphotropic virus 1 and 2 (HTLV-1 and HTLV-2) and human immunodeficiency virus (HIV) [...] Full article
(This article belongs to the Special Issue HTLV-HIV Coinfection)

Research

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16 pages, 4992 KiB  
Article
HTLV-2 Enhances CD8+ T Cell-Mediated HIV-1 Inhibition and Reduces HIV-1 Integrated Proviral Load in People Living with HIV-1
by María Abad-Fernández, Francisco J. Hernández-Walias, María J. Ruiz de León, María J. Vivancos, María J. Pérez-Elías, Ana Moreno, José L. Casado, Carmen Quereda, Fernando Dronda, Santiago Moreno and Alejandro Vallejo
Viruses 2022, 14(11), 2472; https://doi.org/10.3390/v14112472 - 9 Nov 2022
Cited by 3 | Viewed by 3040
Abstract
People living with HIV-1 and HTLV-2 concomitantly show slower CD4+ T cell depletion and AIDS progression, more frequency of the natural control of HIV-1, and lower mortality rates. A similar beneficial effect of this infection has been reported on HCV coinfection reducing [...] Read more.
People living with HIV-1 and HTLV-2 concomitantly show slower CD4+ T cell depletion and AIDS progression, more frequency of the natural control of HIV-1, and lower mortality rates. A similar beneficial effect of this infection has been reported on HCV coinfection reducing transaminases, increasing the spontaneous clearance of HCV infection and delaying the development of hepatic fibrosis. Given the critical role of CD8+ T cells in controlling HIV-1 infection, we analysed the role of CD8+ T cell-mediated cytotoxic activity in coinfected individuals living with HIV-1. One hundred and twenty-eight individuals living with HIV-1 in four groups were studied: two groups with HTLV-2 infection, including individuals with HCV infection (N = 41) and with a sustained virological response (SVR) after HCV treatment (N = 25); and two groups without HTLV-2 infection, including individuals with HCV infection (N = 25) and with a sustained virological response after treatment (N = 37). We found that CD8+ T cell-mediated HIV-1 inhibition in vitro was higher in individuals with HTLV-2. This inhibition activity was associated with a higher frequency of effector memory CD8+ T cells, higher levels of granzyme A and granzyme B cytolytic enzymes, and perforin. Hence, cellular and soluble cytolytic factors may contribute to the lower HIV-1 pre-ART viral load and the HIV-1 proviral load during ART therapy associated with HTLV-2 infection. Herein, we confirmed and expanded previous findings on the role of HTLV-2 in the beneficial effect on the pathogenesis of HIV-1 in coinfected individuals. Full article
(This article belongs to the Special Issue HTLV-HIV Coinfection)
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13 pages, 1137 KiB  
Article
Biomarkers in a Cohort of HIV-Infected Patients Single- or Co-Infected with HTLV-1, HTLV-2, and/or HCV: A Cross-Sectional, Observational Study
by Adele Caterino-de-Araujo, Karoline R. Campos, Luanda M. S. Oliveira and Paula O. Rigato
Viruses 2022, 14(9), 1955; https://doi.org/10.3390/v14091955 - 3 Sep 2022
Cited by 2 | Viewed by 1735
Abstract
HIV, HTLV-1/-2, and HCV share routes of transmission, and such virus co-infections could account for worse outcomes of associated diseases. Measuring cytokines/chemokines, CD4 and CD8 T cells, and HIV viral load (VL) in HIV single-infected and co-infected individuals has prognostic value. We analyzed [...] Read more.
HIV, HTLV-1/-2, and HCV share routes of transmission, and such virus co-infections could account for worse outcomes of associated diseases. Measuring cytokines/chemokines, CD4 and CD8 T cells, and HIV viral load (VL) in HIV single-infected and co-infected individuals has prognostic value. We analyzed such biomarkers in 129 blood samples of HIV-infected individuals matched for age and sex and divided into six groups (G1 (69 HIV); G2 (9 HIV/HTLV-1); G3 (6 HIV/HTLV-2); G4 (11 HIV/HCV); G5 (19 HIV/HCV/HTLV-1); and G6 (15 HIV/HCV/HTLV-2)). Eight cytokines/chemokines from fifteen analytes could be compared. The highest levels of Th1 and pro-inflammatory cytokines were detected in G2 (IFN-γ) and G6 (IL-6 and IL1-β) and of chemokines in G1 (MIG, IP10, RANTES), G4 (MCP1), and G6 (MIP1-β). The highest CD4 cells number and the lowest HIV VL were identified in G3 and the opposite results in G2. Positive correlations between CD4 and CD8 cells counts and IL-6 levels were detected in G2 and G5 and of HIV VL and RANTES in G4. Negative correlations were detected between CD8 and IFN-γ in G4 and HIV VL and RANTES in G6. Despite the small number of the cohort analyzed, and although the cross-sectional study design does not allow firm conclusions, the homogeneity of the characteristics of HIV/HTLV-co-infected individuals regarding age, time and route of HIV acquisition, and criteria for introducing ART enable us to suggest a negative impact of HTLV-1 and a possible protective role of HTLV-2 in HIV infection progression in such patients. Full article
(This article belongs to the Special Issue HTLV-HIV Coinfection)
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28 pages, 3849 KiB  
Article
Dynamics of HIV-1/HTLV-I Co-Infection Model with Humoral Immunity and Cellular Infection
by Noura H. AlShamrani, Matuka A. Alshaikh, Ahmed M. Elaiw and Khalid Hattaf
Viruses 2022, 14(8), 1719; https://doi.org/10.3390/v14081719 - 4 Aug 2022
Cited by 10 | Viewed by 2151
Abstract
Human immunodeficiency virus type 1 (HIV-1) and human T-lymphotropic virus type I (HTLV-I) are two retroviruses which infect the same target, CD4+ T cells. This type of cell is considered the main component of the immune system. Since both viruses have [...] Read more.
Human immunodeficiency virus type 1 (HIV-1) and human T-lymphotropic virus type I (HTLV-I) are two retroviruses which infect the same target, CD4+ T cells. This type of cell is considered the main component of the immune system. Since both viruses have the same means of transmission between individuals, HIV-1-infected patients are more exposed to the chance of co-infection with HTLV-I, and vice versa, compared to the general population. The mathematical modeling and analysis of within-host HIV-1/HTLV-I co-infection dynamics can be considered a robust tool to support biological and medical research. In this study, we have formulated and analyzed an HIV-1/HTLV-I co-infection model with humoral immunity, taking into account both latent HIV-1-infected cells and HTLV-I-infected cells. The model considers two modes of HIV-1 dissemination, virus-to-cell (V-T-C) and cell-to-cell (C-T-C). We prove the nonnegativity and boundedness of the solutions of the model. We find all steady states of the model and establish their existence conditions. We utilize Lyapunov functions and LaSalle’s invariance principle to investigate the global stability of all the steady states of the model. Numerical simulations were performed to illustrate the corresponding theoretical results. The effects of humoral immunity and C-T-C transmission on the HIV-1/HTLV-I co-infection dynamics are discussed. We have shown that humoral immunity does not play the role of clearing an HIV-1 infection but it can control HIV-1 infection. Furthermore, we note that the omission of C-T-C transmission from the HIV-1/HTLV-I co-infection model leads to an under-evaluation of the basic HIV-1 mono-infection reproductive ratio. Full article
(This article belongs to the Special Issue HTLV-HIV Coinfection)
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Review

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31 pages, 1415 KiB  
Review
Co-Infection and Cancer: Host–Pathogen Interaction between Dendritic Cells and HIV-1, HTLV-1, and Other Oncogenic Viruses
by Tania H. Mulherkar, Daniel Joseph Gómez, Grace Sandel and Pooja Jain
Viruses 2022, 14(9), 2037; https://doi.org/10.3390/v14092037 - 14 Sep 2022
Cited by 15 | Viewed by 5311
Abstract
Dendritic cells (DCs) function as a link between innate and adaptive immune responses. Retroviruses HIV-1 and HTLV-1 modulate DCs to their advantage and utilize them to propagate infection. Coinfection of HTLV-1 and HIV-1 has implications for cancer malignancies. Both viruses initially infect DCs [...] Read more.
Dendritic cells (DCs) function as a link between innate and adaptive immune responses. Retroviruses HIV-1 and HTLV-1 modulate DCs to their advantage and utilize them to propagate infection. Coinfection of HTLV-1 and HIV-1 has implications for cancer malignancies. Both viruses initially infect DCs and propagate the infection to CD4+ T cells through cell-to-cell transmission using mechanisms including the formation of virologic synapses, viral biofilms, and conduits. These retroviruses are both neurotrophic with neurovirulence determinants. The neuropathogenesis of HIV-1 and HTLV-1 results in neurodegenerative diseases such as HIV-associated neurocognitive disorders (HAND) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Infected DCs are known to traffic to the brain (CNS) and periphery (PNS, lymphatics) to induce neurodegeneration in HAND and HAM/TSP patients. Elevated levels of neuroinflammation have been correlated with cognitive decline and impairment of motor control performance. Current vaccinations and therapeutics for HIV-1 and HTLV-1 are assessed and can be applied to patients with HIV-1-associated cancers and adult T cell leukemia/lymphoma (ATL). These diseases caused by co-infections can result in both neurodegeneration and cancer. There are associations with cancer malignancies and HIV-1 and HTLV-1 as well as other human oncogenic viruses (EBV, HBV, HCV, HDV, and HPV). This review contains current knowledge on DC sensing of HIV-1 and HTLV-1 including DC-SIGN, Tat, Tax, and current viral therapies. An overview of DC interaction with oncogenic viruses including EBV, Hepatitis viruses, and HPV is also provided. Vaccines and therapeutics targeting host–pathogen interactions can provide a solution to co-infections, neurodegeneration, and cancer. Full article
(This article belongs to the Special Issue HTLV-HIV Coinfection)
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