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

Deadline for manuscript submissions: 30 September 2025 | Viewed by 6937

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Prof. Dr. Carlos Brites

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Guest Editor

Department of Internal Medicine, School of Medicine, Federal University of Bahia, Salvador, BA, Brazil
Interests: HIV; HTLV; human retroviruses
Special Issues, Collections and Topics in MDPI journals

Prof. Dr. Antonio Vallinoto

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Guest Editor

Laboratory of Virology, Institute of Biological Sciences, Federal University of Pará (UFPA), Belém 66075-110, PA, Brazil
Interests: HTLV-1/2; HTLV-associated diseases; human retrovirology; persistent viral infections (HIV, HTLV, HCV, HBV and others)
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Special Issue Information

Dear Colleagues,

The concurrent presence of HIV and HTLV in an individual may give rise to interactions that impact disease progression, presenting challenges in terms of diagnosis, management and treatment. This Special Issue aims to provide insights into the causes and consequences of ongoing HIV and HTLV co-infection in the era of ART. The included studies investigate whether HTLV co-infection may enhance immune activation in individuals living with HIV during antiretroviral therapy (ART) suppression. Additionally, the focus is on exploring whether co-infected individuals face an elevated risk of opportunistic infections. The issue also addresses whether co-infected individuals may pose an increased risk of transmission to others through various routes. Clinical analyses within this Special Issue strive to strike a balance between ART for HIV and potential considerations for HTLV-1 treatment. The information gathered in this issue is expected to be of significant interest and value to the scientific, clinical and public health communities as they navigate the challenges faced by both HIV and HTLV populations.

Prof. Dr. Carlos Brites
Prof. Dr. Antonio Vallinoto
Guest Editors

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Keywords

human T-cell leukemia virus
HIV
HTLV-associated diseases
HIV co-infections

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Published Papers (7 papers)

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Research

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13 pages, 1724 KiB

Open AccessArticle

Toll-Like Receptor Genes and Risk of Latent Tuberculosis Infection in People Infected with HIV-1

by Svetlana Salamaikina, Ekaterina Kulabukhova, Vitaly Korchagin, Olga Khokhlova, Konstantin Mironov and Vasiliy Akimkin

Viruses 2024, 16(9), 1371; https://doi.org/10.3390/v16091371 - 28 Aug 2024

Viewed by 744

Abstract

The purpose of this study was to determine the contribution of genetic factors, i.e., the level of expression and polymorphisms of Toll-like receptors (TLR), to the susceptibility of latent tuberculosis infection in a Russian cohort of individuals infected with HIV. The patients (n = 317) with confirmed HIV infection were divided into two groups according to the results of the STANDARD E TB-Feron test: 63 cases with a latent TB infection and 274 controls without LTBI. Total DNA and RNA were isolated from whole-blood samples. SNP genotyping and expression levels of five TLR genes (TLR1, TLR2, TLR4, TLR6, and TLR8) were determined by means of real-time PCR. There were no significant differences in the expression levels of the TLRs between the case and control groups. In addition, we did not observe any significant association between the analyzed SNPs and the susceptibility of Latent tuberculosis infection (LTBI) in patients with HIV. However, patients from an entire cohort with the rs4986790-GG (TLR4) and rs5743708-GG (TLR2) genotypes were characterized by lower CD4 T-cell counts compared to carriers of alternative alleles. Moreover, we found a significant risk of a hazardous drop in the CD4 T-cell count below 350 cells/mm³ associated with the rs4986790-G (TLR4) allele. Latent tuberculosis infection in individuals infected with HIV does not significantly modify the level of TLR gene expression. Full article

(This article belongs to the Special Issue HIV and HTLV Infections and Coinfections)

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16 pages, 2484 KiB

Open AccessArticle

SARS-CoV-2 Modulation of HIV Latency Reversal in a Myeloid Cell Line: Direct and Bystander Effects

by Patricio Jarmoluk, Franco Agustín Sviercz, Cintia Cevallos, Rosa Nicole Freiberger, Cynthia Alicia López, Guido Poli, M. Victoria Delpino and Jorge Quarleri

Viruses 2024, 16(8), 1310; https://doi.org/10.3390/v16081310 - 17 Aug 2024

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Abstract

Coronavirus disease 2019 (COVID-19) might impact disease progression in people living with HIV (PLWH), including those on effective combination antiretroviral therapy (cART). These individuals often experience chronic conditions characterized by proviral latency or low-level viral replication in CD4+ memory T cells and tissue macrophages. Pro-inflammatory cytokines, such as TNF-α, IL-1β, IL-6, and IFN-γ, can reactivate provirus expression in both primary cells and cell lines. These cytokines are often elevated in individuals infected with SARS-CoV-2, the virus causing COVID-19. However, it is still unknown whether SARS-CoV-2 can modulate HIV reactivation in infected cells. Here, we report that exposure of the chronically HIV-1-infected myeloid cell line U1 to two different SARS-CoV-2 viral isolates (ancestral and BA.5) reversed its latent state after 24 h. We also observed that SARS-CoV-2 exposure of human primary monocyte-derived macrophages (MDM) initially drove their polarization towards an M1 phenotype, which shifted towards M2 over time. This effect was associated with soluble factors released during the initial M1 polarization phase that reactivated HIV production in U1 cells, like MDM stimulated with the TLR agonist resiquimod. Our study suggests that SARS-CoV-2-induced systemic inflammation and interaction with macrophages could influence proviral HIV-1 latency in myeloid cells in PLWH. Full article

(This article belongs to the Special Issue HIV and HTLV Infections and Coinfections)

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15 pages, 1181 KiB

Open AccessArticle

Molecular and Phylogenetic Evidence of Interfamilial Transmission of HTLV-1 in the Afro-Descendant Community of São José de Icatú in the Brazilian Amazon

by Bruno José Sarmento Botelho, Wandrey Roberto dos Santos Brito, Gabriel dos Santos Pereira Neto, Janete Silvana Souza Gonçalves, Bruna Maria Silva Oliveira, Camille Marcela Camarinha de Oliveira, Aline Cecy Rocha de Lima, Sandra Souza Lima, Priscila de Nazaré Quaresma Pinheiro, Felipe Bonfim Freitas, João Farias Guerreiro, Ricardo Ishak, Antonio Carlos Rosário Vallinoto and Izaura M. Vieira Cayres Vallinoto

Viruses 2024, 16(8), 1290; https://doi.org/10.3390/v16081290 - 13 Aug 2024

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Abstract

This study aimed to describe the prevalence of HTLV-1/2 in quilombola communities in the state of Pará and investigate the possible sociodemographic risk factors associated with the infection, as well as to trace the occurrence of the familial transmission of the virus. A total of 310 individuals living in eight quilombos located in the state of Pará (northern Brazil) were investigated for the presence of anti-HTLV-1/2 antibodies using an enzyme-linked immunosorbent assay (ELISA), and positive samples were confirmed using Western blot and/or real-time quantitative polymerase chain reaction (qPCR). Participants answered a questionnaire about sociodemographic aspects and risk factors for infection. Anti-HTLV-1/2 antibodies were detected in two individuals (one man and one woman), for an overall seroprevalence of 0.65%. Both individuals belonged to the community of São José de Icatú. The search for intrafamilial infection identified two other infected women, which increased the general prevalence of HTLV-1 among the Icatú to 6.25% (4/64). Western blot and qPCR confirmed their HTLV-1 infection, and phylogenetic analysis demonstrated that the isolates were of the cosmopolitan subtype and transcontinental subgroup. Epidemiological investigation of the cases revealed that the three women, at some point in their lives, had a relationship with the infected male individual. HTLV-1 is transmitted silently between individuals in the community of São José de Icatú with a present or past family relationship, stressing the need for screening and laboratory diagnosis to prevent further dissemination of the virus and surveillance of disease emergence. Full article

(This article belongs to the Special Issue HIV and HTLV Infections and Coinfections)

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16 pages, 1614 KiB

Open AccessArticle

HIV, HCV and HIV-HCV Coinfections in the General Population versus Inmates from Romania

by Camelia Sultana, Carmine Falanga, Grațiana Chicin, Laurențiu Ion, Camelia Grancea, Daniela Chiriac, Adriana Iliescu and Andrea Gori

Viruses 2024, 16(8), 1279; https://doi.org/10.3390/v16081279 - 10 Aug 2024

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Abstract

The objective of this study was to analyze the epidemiological links of the human immunodeficiency virus (HIV), hepatitis C virus (HCV) and HIV-HCV coinfections to less studied types of transmission in certain populations. We performed an observational, prospective study on 903 patients aged between 15–87 years who took part in the Open Test Project. They were divided in two subgroups: general population vs. individuals from prisons who were questioned about multiple risk factors. A chi-square independence test was used to establish correlations between risk factors and results of screening tests. Logistic regression was used to calculate the probability of a reactive screening test based on each independent risk factor and age. HIV was very strongly associated with unprotected sexual intercourse with HIV-positive partners (the strongest association), unprotected sexual intercourse with sex workers, newly diagnosed sexually transmitted diseases (STDs), intravenous drug users (IDUs) and sharing injecting materials. In the case of HCV reactive tests, very strong associations have been established with IDUs (the strongest association), unprotected sex with IDUs and sharing injecting materials. Our study indicates the need for implementing targeted public health programs, tailored to the local epidemiology that can ultimately lead to micro-elimination of hepatitis and HIV infections in this area. Full article

(This article belongs to the Special Issue HIV and HTLV Infections and Coinfections)

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13 pages, 259 KiB

Open AccessArticle

Prevalence of HTLV-1 and Hepatitis B Surface Antigen (HBsAg) Positivity among MSM Attending a Large HIV Treatment Centre in Trinidad

by Robert Jeffrey Edwards, Selena Todd, Jonathan Edwards, Noreen Jack and Gregory Boyce

Viruses 2024, 16(7), 1169; https://doi.org/10.3390/v16071169 - 20 Jul 2024

Viewed by 971

Abstract

HIV-1, Hepatitis B and HTLV-1 have similar risk factors and shared routes of transmission and MSM are disproportionately affected by HIV. The aim of the study was to determine the prevalence of HTLV-1 and HBsAg positivity at initial enrolment among MSM attending a large HIV Clinic in Trinidad. Chart reviews were conducted between 2 and 15 January 2024, among self-identified MSM and a comparative group of randomly selected self-identified heterosexual males where sociodemographic, clinical and laboratory data were collected and analysed using SPSS Version 25. During the period April 2002–31 October 2023, in total there were 10,424 patients registered at the clinic, of whom 1255 (12.0%) were self-identified MSM, with an age range of 19–85 years and a median age of 40 years. There were 1822 randomly selected heterosexual males, with an age range of 18–94 years old and a median age of 52 years. Among the MSM, there were 21 (1.67%) patients who were HIV-1/HTLV-1-coinfected, 64 (5.10%) who were HIV-1/HBsAg-coinfected and two (0.16%) who were coinfected with all three viruses (HIV-1/HTLV-1/HBsAg) as compared to 47 ((2.58%) HIV-1/HTLV-1-coinfected (p = 0.12), 69 (3.79%) HIV-1/HBsAg-coinfected (p = 0.10) and three (0.16%) patients coinfected with all three viruses among the heterosexual males. There were no patients with HTLV-1-related diseases among the HIV-1/HTLV-1-coinfected patients and there were no deaths from chronic liver disease in patients coinfected with HIV-1/HBsAg. Despite the availability of an efficacious vaccine, there is a prevalence of hepatitis B of 5.1% among MSM attending the HIV Clinic in Trinidad; therefore, programmes to increase health literacy, screening and immunization are urgently needed. Full article

(This article belongs to the Special Issue HIV and HTLV Infections and Coinfections)

18 pages, 3183 KiB

Open AccessArticle

Immunogenetic Profile Associated with Patients Living with HIV-1 and Epstein–Barr Virus (EBV) in the Brazilian Amazon Region

by Iran Barros Costa, Mayara Natália Santana-da-Silva, Patrícia Yuri Nogami, Carolinne de Jesus Santos e Santos, Leonn Mendes Soares Pereira, Eliane dos Santos França, Amaury Bentes Cunha Freire, Francisco Lúzio de Paula Ramos, Talita Antonia Furtado Monteiro, Olinda Macedo, Rita Catarina Medeiros Sousa, Felipe Bonfim Freitas, Antonio Carlos Rosário Vallinoto and Igor Brasil-Costa

Viruses 2024, 16(7), 1012; https://doi.org/10.3390/v16071012 - 24 Jun 2024

Cited by 1 | Viewed by 936

Abstract

Viral coinfection among HIV-positive patients, coupled with the development of AIDS, remains a major public health problem. The synergism between the presence of HIV and other viruses has consequences in relation to changes in the severity of the infection, as well as changes in the natural course of both infections. Several polymorphisms present in genes that encode cytokines have a relevant influence on their transcription and consequently on the production of such immunological molecules. The present study evaluated the influence of SNPs located in the promoter regions of genes encoding the cytokines INF-ɣ, TNF, IL-6, IL-4, and IL-2, as well as their respective plasma concentrations, in patients infected with HIV and/or EBV in the state of Pará. Additionally, this study described the epidemiological profile and compared CD4+ and CD8+ T lymphocyte counts among the groups studied. The associative analysis between the SNPs and plasma cytokine concentrations in different groups showed statistical relevance for three polymorphisms: rs2069762 (IL2), where the GG genotype demonstrated higher IL-2 levels in HIV mono-infected individuals; rs2243250 (IL4), where the CT genotype showed higher IL-4 levels in the control group; and rs2069705 (IFNG), where the TT genotype showed higher IFN-γ levels in the coinfected group. Regarding SNP associations with CD4+/CD8+ counts, significant findings were observed in HIV mono-infected individuals: the rs2069705 (IFNG) polymorphism was linked to higher CD4+ counts with the CT genotype, and rs1799964 (TNF) was associated with higher CD8+ counts with the CC genotype. Therefore, this study provides evidence that the rs2069705 (IFNG) SNP is associated with elevated IFN-γ levels, which may have pathogenic consequences, as depletion of this cytokine is concerning for people living with HIV due to its antiviral properties. Full article

(This article belongs to the Special Issue HIV and HTLV Infections and Coinfections)

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41 pages, 2642 KiB

Open AccessReview

Current State of Therapeutics for HTLV-1

by Tiana T. Wang, Ashley Hirons, Marcel Doerflinger, Kevin V. Morris, Scott Ledger, Damian F. J. Purcell, Anthony D. Kelleher and Chantelle L. Ahlenstiel

Viruses 2024, 16(10), 1616; https://doi.org/10.3390/v16101616 - 15 Oct 2024

Viewed by 935

Abstract

Human T cell leukaemia virus type-1 (HTLV-1) is an oncogenic retrovirus that causes lifelong infection in ~5–10 million individuals globally. It is endemic to certain First Nations populations of Northern and Central Australia, Japan, South and Central America, Africa, and the Caribbean region. HTLV-1 preferentially infects CD4⁺ T cells and remains in a state of reduced transcription, often being asymptomatic in the beginning of infection, with symptoms developing later in life. HTLV-1 infection is implicated in the development of adult T cell leukaemia/lymphoma (ATL) and HTLV-1-associated myelopathies (HAM), amongst other immune-related disorders. With no preventive or curative interventions, infected individuals have limited treatment options, most of which manage symptoms. The clinical burden and lack of treatment options directs the need for alternative treatment strategies for HTLV-1 infection. Recent advances have been made in the development of RNA-based antiviral therapeutics for Human Immunodeficiency Virus Type-1 (HIV-1), an analogous retrovirus that shares modes of transmission with HTLV-1. This review highlights past and ongoing efforts in the development of HTLV-1 therapeutics and vaccines, with a focus on the potential for gene therapy as a new treatment modality in light of its successes in HIV-1, as well as animal models that may help the advancement of novel antiviral and anticancer interventions. Full article

(This article belongs to the Special Issue HIV and HTLV Infections and Coinfections)

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