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14 pages, 1459 KiB

Open AccessArticle

Clinical Significance of Elevated KSHV Viral Load in HIV-Related Kaposi’s Sarcoma Patients in South Africa

by Rebecca Monica Tibenderana, Melissa Jayne Blumenthal, Emmanuel Bukajumbe, Georgia Schäfer and Zainab Mohamed

Viruses 2024, 16(2), 189; https://doi.org/10.3390/v16020189 - 26 Jan 2024

Viewed by 928

Abstract

Kaposi’s sarcoma (KS) is an AIDS-defining illness caused by Kaposi’s sarcoma-associated herpesvirus (KSHV) predominantly in the context of HIV-related immune suppression. We aimed to explore the usefulness of KSHV DNA viral load (VL) measurement in predicting the severity, response to treatment and outcome [...] Read more.

Kaposi’s sarcoma (KS) is an AIDS-defining illness caused by Kaposi’s sarcoma-associated herpesvirus (KSHV) predominantly in the context of HIV-related immune suppression. We aimed to explore the usefulness of KSHV DNA viral load (VL) measurement in predicting the severity, response to treatment and outcome of KS. We retrospectively assessed a cohort of KS patients (n = 94) receiving treatment at Groote Schuur Hospital, Cape Town, South Africa. Demographic and clinical data, KS staging and response to treatment were extracted from patient files, while long-term survival was ascertained from hospital records. KSHV serology and VL and hIL-6 were determined empirically from patients’ blood. All patients were HIV-positive adults, the majority of whom were on HAART at the time of recruitment. KSHV VL was detectable in 65 patients’ blood (median: 280.5/10⁶ cells (IQR: 69.7–1727.3)) and was highest in patients with S1 HIV-related systemic disease (median 1066.9/10⁶ cells, IQR: 70.5–11,269.6). KSHV VL was associated with the S1 stage in a binomial regression controlling for confounders (adjusted odds ratio 5.55, 95% CI: 1.28–24.14, p = 0.022). A subset of six patients identified to have extremely high KSHV VLs was predominantly T₁ stage with pulmonary KS, and most had died at follow-up. In our cohort, elevated KSHV VL is associated with systemic HIV-related illness in KS disease. Extremely high KSHV VLs warrant further investigation for patients potentially requiring intensive treatment and investigation for progression or diagnosis of concurrent KSHV lytic syndromes. Full article

(This article belongs to the Special Issue State-of-the-Art Virology Research in South Africa)

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22 pages, 3078 KiB

Open AccessArticle

Cervicovaginal Human Papillomavirus Genomes, Microbiota Composition and Cytokine Concentrations in South African Adolescents

by Anna-Ursula Happel, Christina Balle, Enock Havyarimana, Bryan Brown, Brandon S. Maust, Colin Feng, Byung H. Yi, Katherine Gill, Linda-Gail Bekker, Jo-Ann S. Passmore, Heather B. Jaspan and Arvind Varsani

Viruses 2023, 15(3), 758; https://doi.org/10.3390/v15030758 - 15 Mar 2023

Cited by 1 | Viewed by 1988

Abstract

The interaction between cervicovaginal virome, bacteriome and genital inflammation has not been extensively investigated. We assessed the vaginal DNA virome from 33 South African adolescents (15–19 years old) using shotgun DNA sequencing of purified virions. We present analyses of eukaryote-infecting DNA viruses, with [...] Read more.

The interaction between cervicovaginal virome, bacteriome and genital inflammation has not been extensively investigated. We assessed the vaginal DNA virome from 33 South African adolescents (15–19 years old) using shotgun DNA sequencing of purified virions. We present analyses of eukaryote-infecting DNA viruses, with a focus on human papillomavirus (HPV) genomes and relate these to the vaginal bacterial microbiota (assessed by 16S rRNA gene sequencing) and cytokines (assessed by Luminex). The DNA virome included single-stranded (Anelloviridae, Genomoviridae) and double-stranded DNA viruses (Adenoviridae, Alloherpesviridae, Herpesviridae, Marseilleviridae, Mimiviridae, Polyomaviridae, Poxviridae). We identified 110 unique, complete HPV genomes within two genera (Alphapapillomavirus and Gammapapillomavirus) representing 40 HPV types and 12 species. Of the 40 HPV types identified, 35 showed positive co-infection patterns with at least one other type, mainly HPV-16. HPV-35, a high-risk genotype currently not targeted by available vaccines, was the most prevalent HPV type identified in this cohort. Bacterial taxa commonly associated with bacterial vaginosis also correlated with the presence of HPV. Bacterial vaginosis, rather than HPV, was associated with increased genital inflammation. This study lays the foundation for future work characterizing the vaginal virome and its role in women’s health. Full article

(This article belongs to the Special Issue State-of-the-Art Virology Research in South Africa)

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16 pages, 1372 KiB

Open AccessArticle

Detection and Characterization of an H9N2 Influenza A Virus in the Egyptian Rousette Bat in Limpopo, South Africa

by Rochelle Rademan, Marike Geldenhuys and Wanda Markotter

Viruses 2023, 15(2), 498; https://doi.org/10.3390/v15020498 - 10 Feb 2023

Cited by 4 | Viewed by 2204

Abstract

In recent years, bats have been shown to host various novel bat-specific influenza viruses, including H17N10 and H18N11 in the Americas and the H9N2 subtype from Africa. Rousettus aegyptiacus (Egyptian Rousette bat) is recognized as a host species for diverse viral agents. This [...] Read more.

In recent years, bats have been shown to host various novel bat-specific influenza viruses, including H17N10 and H18N11 in the Americas and the H9N2 subtype from Africa. Rousettus aegyptiacus (Egyptian Rousette bat) is recognized as a host species for diverse viral agents. This study focused on the molecular surveillance of a maternal colony in Limpopo, South Africa, between 2017–2018. A pan-influenza hemi-nested RT-PCR assay targeting the PB1 gene was established, and influenza A virus RNA was identified from one fecal sample out of 860 samples. Genome segments were recovered using segment-specific amplification combined with standard Sanger sequencing and Illumina unbiased sequencing. The identified influenza A virus was closely related to the H9N2 bat-influenza virus, confirming the circulation of this subtype among Egyptian fruit bat populations in Southern Africa. This bat H9N2 subtype contained amino acid residues associated with transmission and virulence in either mammalian or avian hosts, though it will likely require additional adaptations before spillover. Full article

(This article belongs to the Special Issue State-of-the-Art Virology Research in South Africa)

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14 pages, 1158 KiB

Open AccessArticle

Host-Associated Distribution of Two Novel Mammarenaviruses in Rodents from Southern Africa

by Marike Geldenhuys, Jacqueline Weyer, Teresa Kearney and Wanda Markotter

Viruses 2023, 15(1), 99; https://doi.org/10.3390/v15010099 - 29 Dec 2022

Cited by 1 | Viewed by 1218

Abstract

Mammarenaviruses are hosted by several rodent species, a small number of which have been known to be zoonotic. Host surveillance among small mammals has identified a large diversity of previously undescribed mammarenaviruses. Intensified biosurveillance is warranted to better understand the diversity of these [...] Read more.

Mammarenaviruses are hosted by several rodent species, a small number of which have been known to be zoonotic. Host surveillance among small mammals has identified a large diversity of previously undescribed mammarenaviruses. Intensified biosurveillance is warranted to better understand the diversity of these agents. Longitudinal host surveillance involving non-volant small mammals at a site in the Limpopo province, South Africa, was conducted. The study reports on the screening results of 563 samples for the presence of mammarenavirus RNA. PCR-positive samples were subjected to sequencing using Miseq amplicon sequencing. Sequences with close similarity to Mariental and Lunk viruses were identified from two rodent species, Micaelamys namaquensis and Mus minutoides. This represents the first description of these viruses from South Africa. The genomic sequences reported here partially satisfied the requirements put forward by the International Committee on the Taxonomy of Viruses’ criteria for species delineation, suggesting that these may be new strains of existing species. The known distribution of these mammarenaviruses is thus expanded further south in Africa. Full article

(This article belongs to the Special Issue State-of-the-Art Virology Research in South Africa)

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16 pages, 2618 KiB

Open AccessArticle

Evaluation of the HIV-1 Polymerase Gene Sequence Diversity for Prediction of Recent HIV-1 Infections Using Shannon Entropy Analysis

by Paballo Nkone, Shayne Loubser, Thomas C. Quinn, Andrew D. Redd, Oliver Laeyendecker, Caroline T. Tiemessen and Simnikiwe H. Mayaphi

Viruses 2022, 14(7), 1587; https://doi.org/10.3390/v14071587 - 21 Jul 2022

Cited by 2 | Viewed by 1511

Abstract

HIV-1 incidence is an important parameter for assessing the impact of HIV-1 interventions. The aim of this study was to evaluate HIV-1 polymerase (pol) gene sequence diversity for the prediction of recent HIV-1 infections. Complete pol Sanger sequences obtained from 45 [...] Read more.

HIV-1 incidence is an important parameter for assessing the impact of HIV-1 interventions. The aim of this study was to evaluate HIV-1 polymerase (pol) gene sequence diversity for the prediction of recent HIV-1 infections. Complete pol Sanger sequences obtained from 45 participants confirmed to have recent or chronic HIV-1 infection were used. Shannon entropy was calculated for amino acid (aa) sequences for the entire pol and for sliding windows consisting of 50 aa each. Entropy scores for the complete HIV-1 pol were significantly higher in chronic compared to recent HIV-1 infections (p < 0.0001) and the same pattern was observed for some sliding windows (p-values ranging from 0.011 to <0.001), leading to the identification of some aa mutations that could discriminate between recent and chronic infection. Different aa mutation groups were assessed for predicting recent infection and their performance ranged from 64.3% to 100% but had a high false recency rate (FRR), which was decreased to 19.4% when another amino acid mutation (M456) was included in the analysis. The pol-based molecular method identified in this study would not be ideal for use on its own due to high FRR; however, this method could be considered for complementing existing serological assays to further reduce FRR. Full article

(This article belongs to the Special Issue State-of-the-Art Virology Research in South Africa)

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18 pages, 696 KiB

Open AccessArticle

SARS-CoV-2 Infection Is Associated with Uncontrolled HIV Viral Load in Non-Hospitalized HIV-Infected Patients from Gugulethu, South Africa

by Humaira Lambarey, Melissa J. Blumenthal, Abeen Chetram, Wendy Joyimbana, Lauren Jennings, Marius B. Tincho, Wendy A. Burgers, Catherine Orrell and Georgia Schäfer

Viruses 2022, 14(6), 1222; https://doi.org/10.3390/v14061222 - 03 Jun 2022

Cited by 5 | Viewed by 2644

Abstract

In South Africa, high exposure to SARS-CoV-2 occurs primarily in densely populated, low-income communities, which are additionally burdened by highly prevalent Human Immunodeficiency Virus (HIV). With the aim to assess SARS-CoV-2 seroprevalence and its association with HIV-related clinical parameters in non-hospitalized patients likely [...] Read more.

In South Africa, high exposure to SARS-CoV-2 occurs primarily in densely populated, low-income communities, which are additionally burdened by highly prevalent Human Immunodeficiency Virus (HIV). With the aim to assess SARS-CoV-2 seroprevalence and its association with HIV-related clinical parameters in non-hospitalized patients likely to be highly exposed to SARS-CoV-2, this observational cross-sectional study was conducted at the Gugulethu Community Health Centre Antiretroviral clinic between October 2020 and June 2021, after the first COVID-19 wave in South Africa and during the second and beginning of the third wave. A total of 150 adult (median age 39 years [range 20–65 years]) HIV-infected patients (69% female; 31% male) were recruited. 95.3% of the cohort was on antiretroviral therapy (ART), had a median CD4 count of 220 cells/µL (range 17–604 cells/µL) and a median HIV viral load (VL) of 49 copies/mL (range 1–1,050,867 copies/mL). Furthermore, 106 patients (70.7%) were SARS-CoV-2 seropositive, and 0% were vaccinated. When stratified for HIV VL, patients with uncontrolled HIV viremia (HIV VL > 1000 copies/mL) had significantly higher odds of SARS-CoV-2 seropositivity than patients with HIV VL < 1000 copies/mL, after adjusting for age, sex and ART status (p = 0.035, adjusted OR 2.961 [95% CI: 1.078–8.133]). Although the cause–effect relationship could not be determined due to the cross-sectional study design, these results point towards a higher risk of SARS-CoV-2 susceptibility among viremic HIV patients, or impaired HIV viral control due to previous co-infection with SARS-CoV-2. Full article

(This article belongs to the Special Issue State-of-the-Art Virology Research in South Africa)

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13 pages, 890 KiB

Open AccessArticle

Complexity of Human Cytomegalovirus Infection in South African HIV-Exposed Infants with Pneumonia

by Kerusha Govender, Raveen Parboosing, Salvatore Camiolo, Petr Hubáček, Irene Görzer, Elisabeth Puchhammer-Stöckl and Nicolás M. Suárez

Viruses 2022, 14(5), 855; https://doi.org/10.3390/v14050855 - 21 Apr 2022

Viewed by 1671

Abstract

Human cytomegalovirus (HCMV) can cause significant end-organ diseases such as pneumonia in HIV-exposed infants. Complex viral factors may influence pathogenesis including: a large genome with a sizeable coding capacity, numerous gene regions of hypervariability, multiple-strain infections, and tissue compartmentalization of strains. We used [...] Read more.

Human cytomegalovirus (HCMV) can cause significant end-organ diseases such as pneumonia in HIV-exposed infants. Complex viral factors may influence pathogenesis including: a large genome with a sizeable coding capacity, numerous gene regions of hypervariability, multiple-strain infections, and tissue compartmentalization of strains. We used a whole genome sequencing approach to assess the complexity of infection by comparing high-throughput sequencing data obtained from respiratory and blood specimens of HIV-exposed infants with severe HCMV pneumonia with those of lung transplant recipients and patients with hematological disorders. There were significantly more specimens from HIV-exposed infants showing multiple HCMV strain infection. Some genotypes, such as UL73 G4B and UL74 G4, were significantly more prevalent in HIV-exposed infants with severe HCMV pneumonia. Some genotypes were predominant in the respiratory specimens of several patients. However, the predominance was not statistically significant, precluding firm conclusions on anatomical compartmentalization in the lung. Full article

(This article belongs to the Special Issue State-of-the-Art Virology Research in South Africa)

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13 pages, 1780 KiB

Open AccessArticle

Persistent Hepatitis B Viraemia with Polymerase Mutations among HIV/HBV Co-Infected Patients on HBV-Active ART in KwaZulu-Natal, South Africa

by Nokukhanya Msomi, Raveen Parboosing, Eduan Wilkinson, Jennifer Giandhari, Kerusha Govender, Benjamin Chimukangara and Koleka P. Mlisana

Viruses 2022, 14(4), 788; https://doi.org/10.3390/v14040788 - 10 Apr 2022

Cited by 4 | Viewed by 2244

Abstract

To understand the problem of persistent Hepatitis B virus (HBV) viraemia in HIV/HBV co-infected patients on HBV-active antiretroviral therapy (ART), we assessed the rate of HBV virological response in patients on HBV-active ART in KwaZulu-Natal, South Africa, and analysed factors associated with persistent [...] Read more.

To understand the problem of persistent Hepatitis B virus (HBV) viraemia in HIV/HBV co-infected patients on HBV-active antiretroviral therapy (ART), we assessed the rate of HBV virological response in patients on HBV-active ART in KwaZulu-Natal, South Africa, and analysed factors associated with persistent HBV viraemia. One hundred and fifty eligible participants with a chronic HBV diagnosis, with or without HIV coinfection, were enrolled and followed up after 6 months. The HBV pol gene was sequenced by next-generation sequencing and mutations were determined using the Stanford HBVseq database. Logistic regression analysis was used to assess factors associated with HBV viraemia at 6-month follow-up. The mean duration of HBV-active ART was 24 months. Thirty-seven of one hundred and six (35%) participants receiving HBV-active ART for longer than 6 months had virological failure. Advanced immunosuppression with CD4+ cell counts <200 cells/μL was independently associated with persistent HBV viraemia, aOR 5.276 (95% CI 1.575–17.670) p = 0.007. A high proportion of patients on HBV-active ART are unsuppressed, which will ultimately have an impact on global elimination goals. Better monitoring should be implemented, especially in HIV-coinfected patients with low CD4+ cell counts and followed by early HBV drug-resistance testing. Full article

(This article belongs to the Special Issue State-of-the-Art Virology Research in South Africa)

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Review

Jump to: Research

22 pages, 706 KiB

Open AccessReview

Hepatitis B Virus Research in South Africa

by Mohube B. Maepa, Abdullah Ely, Anna Kramvis, Kristie Bloom, Kubendran Naidoo, Omphile E. Simani, Tongai G. Maponga and Patrick Arbuthnot

Viruses 2022, 14(9), 1939; https://doi.org/10.3390/v14091939 - 31 Aug 2022

Cited by 8 | Viewed by 3048

Abstract

Despite being vaccine-preventable, hepatitis B virus (HBV) infection remains the seventh leading cause of mortality in the world. In South Africa (SA), over 1.9 million people are chronically infected with HBV, and 70% of all Black chronic carriers are infected with HBV subgenotype [...] Read more.

Despite being vaccine-preventable, hepatitis B virus (HBV) infection remains the seventh leading cause of mortality in the world. In South Africa (SA), over 1.9 million people are chronically infected with HBV, and 70% of all Black chronic carriers are infected with HBV subgenotype A1. The virus remains a significant burden on public health in SA despite the introduction of an infant immunization program implemented in 1995 and the availability of effective treatment for chronic HBV infection. In addition, the high prevalence of HIV infection amplifies HBV replication, predisposes patients to chronicity, and complicates management of the infection. HBV research has made significant progress leading to better understanding of HBV epidemiology and management challenges in the SA context. This has led to recent revision of the national HBV infection management guidelines. Research on developing new vaccines and therapies is underway and progress has been made with designing potentially curative gene therapies against HBV. This review summarizes research carried out in SA on HBV molecular biology, epidemiology, treatment, and vaccination strategies. Full article

(This article belongs to the Special Issue State-of-the-Art Virology Research in South Africa)

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