scholarly journals Immune Correlates of Disease Progression in Linked HIV-1 Infection

Author(s):  
Michael Tuen ◽  
Jude S Bimela ◽  
Andrew N Banin ◽  
Shilei Ding ◽  
Gordon W Harkins ◽  
...  
2019 ◽  
Vol 10 ◽  
Author(s):  
Michael Tuen ◽  
Jude S. Bimela ◽  
Andrew N. Banin ◽  
Shilei Ding ◽  
Gordon W. Harkins ◽  
...  

2015 ◽  
Vol 13 (6) ◽  
pp. 448-461 ◽  
Author(s):  
Natacha Merindol ◽  
Lionel Berthoux

2013 ◽  
Vol 94 (1) ◽  
pp. 20-29 ◽  
Author(s):  
Elly Baan ◽  
Renée M. van der Sluis ◽  
Margreet E. Bakker ◽  
Vincent Bekker ◽  
Dasja Pajkrt ◽  
...  

The human immunodeficiency virus type 1 (HIV-1) envelope protein provides the primary contact between the virus and host, and is the main target of the adaptive humoral immune response. The length of gp120 variable loops and the number of N-linked glycosylation events are key determinants for virus infectivity and immune escape, while the V3 loop overall positive charge is known to affect co-receptor tropism. We selected two families in which both parents and two children had been infected with HIV-1 for nearly 10 years, but who demonstrated variable parameters of disease progression. We analysed the gp120 envelope sequence and compared individuals that progressed to those that did not in order to decipher evolutionary alterations that are associated with disease progression when individuals are infected with genetically related virus strains. The analysis of the V3-positive charge demonstrated an association between higher V3-positive charges with disease progression. The ratio between the amino acid length and the number of potential N-linked glycosylation sites was also shown to be associated with disease progression with the healthier family members having a lower ratio. In conclusion in individuals initially infected with genetically linked virus strains the V3-positive charges and N-linked glycosylation are associated with HIV-1 disease progression and follow varied evolutionary paths for individuals with varied disease progression.


Vaccines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 260
Author(s):  
Stefania Dispinseri ◽  
Mariangela Cavarelli ◽  
Monica Tolazzi ◽  
Anna Maria Plebani ◽  
Marianne Jansson ◽  
...  

The antibodies with different effector functions evoked by Human Immunodeficiency Virus type 1 (HIV-1) transmitted from mother to child, and their role in the pathogenesis of infected children remain unresolved. So, too, the kinetics and breadth of these responses remain to be clearly defined, compared to those developing in adults. Here, we studied the kinetics of the autologous and heterologous neutralizing antibody (Nab) responses, in addition to antibody-dependent cellular cytotoxicity (ADCC), in HIV-1 infected children with different disease progression rates followed from close after birth and five years on. Autologous and heterologous neutralization were determined by Peripheral blood mononuclear cells (PBMC)- and TZMbl-based assays, and ADCC was assessed with the GranToxiLux assay. The reactivity to an immunodominant HIV-1 gp41 epitope, and childhood vaccine antigens, was assessed by ELISA. Newborns displayed antibodies directed towards the HIV-1 gp41 epitope. However, antibodies neutralizing the transmitted virus were undetectable. Nabs directed against the transmitted virus developed usually within 12 months of age in children with slow progression, but rarely in rapid progressors. Thereafter, autologous Nabs persisted throughout the follow-up of the slow progressors and induced a continuous emergence of escape variants. Heterologous cross-Nabs were detected within two years, but their subsequent increase in potency and breadth was mainly a trait of slow progressors. Analogously, titers of antibodies mediating ADCC to gp120 BaL pulsed target cells increased in slow progressors during follow-up. The kinetics of antibody responses to the immunodominant viral antigen and the vaccine antigens were sustained and independent of disease progression. Persistent autologous Nabs triggering viral escape and an increase in the breadth and potency of cross-Nabs are exclusive to HIV-1 infected slowly progressing children.


2020 ◽  
Vol 2020 ◽  
pp. 1-16
Author(s):  
Ross Cromarty ◽  
Derseree Archary

The relationship between inflammation and HIV has been a focus of research over the last decade. In HIV-infected individuals, increased HIV-associated immune activation significantly correlated to disease progression. While genital inflammation (GI) has been shown to significantly increase the risk of HIV acquisition and transmission, immune correlates for reduced risk remain limited. In certain HIV-exposed seronegative individuals, an immune quiescent phenotype characterized reduced risk. Immune quiescence is defined by specific, targeted, highly regulated immune responses that hinder overt inflammation or immune activation. Targeted management of inflammation, therefore, is a plausible strategy to mitigate HIV risk and slow disease progression. Nonsteroidal anti-inflammatory drugs (NSAIDs) such as hydroxychloroquine and aspirin have shown encouraging preliminary results in low-risk women by reducing systemic and genital immune activation. A topical NSAID, containing ibuprofen, is effective in treating vulvovaginal inflammation. Additionally, the glucocorticoids (GCs), prednisolone, and dexamethasone are used to treat HIV-associated immune activation. Collectively, these data inform on immune-modulating drugs to reduce HIV risk. However, the prolonged use of these pharmaceutical drugs is associated with adverse effects, both systemically and to a lesser extent topically. Natural products with their reduced side effects coupled with anti-inflammatory properties render them viable options. Lactic acid (LA) has immunomodulatory properties. LA regulates the genital microbiome by facilitating the growth of Lactobacillus species, while simultaneously limiting bacterial species that cause microbial dysbiosis and GI. Glycerol monolaurate, besides being anti-inflammatory, also inhibited SIV infections in rhesus macaques. The proposed pharmaceutical and natural products could be used in combination with either antiretrovirals for treatment or preexposure prophylaxis for HIV prevention. This review provides a summary on the associations between inflammation, HIV risk, and disease progression. Furthermore, we use the knowledge from immune quiescence to exploit the use of pharmaceutical and natural products as strategic interventions to manage inflammation, toward mitigating HIV infections.


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