IL-15/IL-15Ra Synergies with IL-12 to Induce Functional CD8 T Cells and NK Cells During Chronic SHIV Infection.

Cytokines are key mediators of immune regulation, orchestrate communication between immune cells, and play a pivotal role in shaping the immune landscape during chronic infection and cancer. The therapeutic potential of IL-15/IL-15Rα and IL-12 has been explored individually in various immunotherapeutic strategies, though not as a combination. Therefore, we investigated whether the combination of IL-15/IL-15Rα and IL-12 treatment would enhance the potency and quality of either NK cells, SIV-specific CD8 T cells, or both, compared with single cytokine treatment.

Lymph node CXCR5+ NK cells associate with control of chronic SHIV infection.

The persistence of virally infected cells as reservoirs despite effective antiretroviral therapy is a major barrier to an HIV/SIV cure. These reservoirs are predominately contained within cells present in the B cell follicles (BCFs) of secondary lymphoid tissues, a site that is characteristically difficult for most cytolytic antiviral effector cells to penetrate. Here, we identified a population of NK cells in macaque lymph nodes that expressed BCF-homing receptor CXCR5 and accumulated within BCFs during chronic SHIV infection.

Trans cohort metabolic reprogramming towards glutaminolysis in long-term successfully treated HIV-infection.

Despite successful combination antiretroviral therapy (cART), persistent low-grade immune activation together with inflammation and toxic antiretroviral drugs can lead to long-lasting metabolic flexibility and adaptation in people living with HIV (PLWH). Our study investigated alterations in the plasma metabolic profiles by comparing PLWH on long-term cART(>5 years) and matched HIV-negative controls (HC) in two cohorts from low- and middle-income countries (LMIC), Cameroon, and India, respectively, to understand the system-level dysregulation in HIV-infection. Using untargeted and targeted LC-MS/MS-based metabolic profiling and applying advanced system biology methods, an altered amino acid metabolism, more specifically to glutaminolysis in PLWH than HC were reported.

Plasma Metabolic Signature and Abnormalities in HIV-Infected Individuals on Long-Term Successful Antiretroviral Therapy.

Targeted metabolomics studies reported metabolic abnormalities in both treated and untreated people living with human immunodeficiency virus (HIV) (PLHIV). The present study aimed to understand the plasma metabolomic changes and predicted the risk of accelerated aging in PLHIV on long-term suppressive antiretroviral therapy (ART) in a case-control study setting and its association with the plasma proteomics biomarkers of inflammation and neurological defects. Plasma samples were obtained from PLHIV on successful long-term ART for more than five years ( = 22) and matched HIV-negative healthy individuals ( = 22, HC herein).

Systemic Inflammation and the Increased Risk of Inflamm-Aging and Age-Associated Diseases in People Living With HIV on Long Term Suppressive Antiretroviral Therapy.

The ART program in low- and middle-income countries (LMIC) like India, follows a public health approach with a standardized regimen for all people living with HIV (PLHIV). Based on the evidence from high-income countries (HIC), the risk of an enhanced, and accentuated onset of premature-aging or age-related diseases has been observed in PLHIV. However, very limited data is available on residual inflammation and immune activation in the populations who are on first-generation anti-HIV drugs like zidovudine and lamivudine that have more toxic side effects.

Cross Type Neutralizing Antibodies Detected in a Unique HIV-2 Infected Individual From India.

Infection with HIV-2, a retrovirus that is closely related to HIV-1, is characterized by slower disease progression and transmission, longer latency period and low or undetectable viremia. Host immunity, including production of potent neutralizing antibodies, may be one of the possible contributors to the distinction between the two infections. In an attempt to understand whether HIV-2 infection results in production of neutralizing antibodies and to characterize the nature of the neutralization response we screened plasma of 37 HIV-2 infected individuals for the presence of broadly neutralizing antibodies.

Mapping of Neutralizing Antibody Epitopes on the Envelope of Viruses Obtained from Plasma Samples Exhibiting Broad Cross-Clade Neutralization Potential Against HIV-1.

Several broadly neutralizing antibodies (bNAbs) that can target HIV strains with large degrees of variability have recently been identified. However, efforts to induce synthesis of such bNAbs that can protect against HIV infection have not met with much success. Identification of specific epitopes encoded in the HIV-1 envelope (Env) that can direct the host to synthesize bNAbs remains a challenge.

Molecular Characteristics of the Envelope of Vertically Transmitted HIV-1 Strains from Infants with HIV Infection.

Mother-to-child transmission (MTCT) of HIV offers a good opportunity to study the dynamics of early viral evolution in the host environment to which the virus has partially adapted. Such studies would throw light on the unique features of the infecting viruses, which will subsequently help to design preventive or therapeutic measures against the newly infecting and evolving strains of HIV. Therefore, we undertook a study to determine the genetic divergence of proviral envelope sequences from the HIV-infected infants (<2 years).