HIV-2 as a model to identify a functional HIV cure

Abstract

Two HIV virus types exist: HIV-1 is pandemic and aggressive, whereas HIV-2 is confined mainly to West Africa and less pathogenic. Despite the fact that it has been almost 40 years since the discovery of AIDS, there is still no cure or vaccine against HIV. Consequently, the concepts of functional vaccines and cures that aim to limit HIV disease progression and spread by persistent control of viral replication without life-long treatment have been suggested as more feasible options to control the HIV pandemic. To identify virus-host mechanisms that could be targeted for functional cure development, researchers have focused on a small fraction of HIV-1 infected individuals that control their infection spontaneously, so-called elite controllers. However, these efforts have not been able to unravel the key mechanisms of the infection control. This is partly due to lack in statistical power since only 0.15% of HIV-1 infected individuals are natural elite controllers. The proportion of long-term viral control is larger in HIV-2 infection compared with HIV-1 infection. We therefore present the idea of using HIV-2 as a model for finding a functional cure against HIV. Understanding the key differences between HIV-1 and HIV-2 infections, and the cross-reactive effects in HIV-1/HIV-2 dual-infection could provide novel insights in developing functional HIV cures and vaccines.

Role of Circulating T Follicular Helper Cells and Stem-Like Memory CD4+ T Cells in the Pathogenesis of HIV-2 Infection and Disease Progression

“…Tscm cells are a small subset of T cells possessing self-renewal capabilities, that when stimulated via the T cell receptor, may divide into mature memory or effector T cells (49,51). Many studies have consistently reported a close and robust association between the proliferation of effector cells and memory T cells and virus control in HIV infection (1,2,52). However, there is a lack of clarity in this line with regard to HIV-2 infection due to the limited number of studies in HIV-2 individuals.…”

“…Acquired immunodeficiency in humans is caused by two types of human immunodeficiency virus (HIV), namely HIV-1 and HIV-2 (1). HIV-2 is less pathogenic than HIV-1, the course of disease is slower, and the proportion of disease controllers is significantly greater with HIV-2 infection (2).…”

Viral reservoirs in elite controllers of HIV-1 infection: Implications for HIV cure strategies

“…More recently, a patient who was infected with a vpr-defective HIV-1 molecular clone and became an EC has been described [8] and members of a transmission cluster of ECs have been found to be infected with HIV-1 isolates that contain related attenuated env genes [9] . Furthermore, the high percentage of people living with HIV-2 who become controllers suggests that viral factors may play a role in clinical outcomes [10] . Taken together, such studies suggest that infection with attenuated or defective viruses can lead to elite control, but they do not indicate that all ECs are infected with defective virus.…”

HIV-2-Infected Macrophages Produce and Accumulate Poorly Infectious Viral Particles

“…Both viruses share comparable genetic organization, structural architecture, and most virological features. Despite this close relationship, the clinical progression of HIV-2 to AIDS is much slower compared to HIV-1 and may reflect better immune control of the infection ( Marlink et al, 1994 ; Nyamweya et al, 2013 ; Esbjörnsson et al, 2019 ). A much larger proportion of people with HIV-2 infection exhibit long-term viral control without ART than is seen in HIV-1 infection ( van der Loeff et al, 2010 ).…”

“…Although, it is estimated that 30–40% of HIV-2 infected people have low or undetectable viral loads ( van der Loeff et al, 2010 ), ongoing viral replication still occurs in HIV-2-infected patients ( Soares et al, 2011 ; Fernandes et al, 2014 ). However, a recent longitudinal study indicates that without ART treatment, HIV-2-infected individuals have still a high probability of developing and dying from AIDS despite the longer time to progress ( Esbjörnsson et al, 2019 ).…”