SIV Evolutionary Dynamics in Cynomolgus Macaques during SIV-Mycobacterium tuberculosis Co-Infection.

Kaho H Tisthammer,Tara Rutledge,Sergio Ita,Collin R Diedrich,Christopher Kline,Pleuni S Pennings,Zandrea Ambrose,Philana Ling Lin

doi:10.3390/v14010048

Kaho H Tisthammer, Tara Rutledge + Show 6 more

Open Access

https://doi.org/10.3390/v14010048

Copy DOI

Abstract

Co-infection with Mycobacterium tuberculosis (Mtb) and human immunodeficiency virus (HIV) is a worldwide public health concern, leading to worse clinical outcomes caused by both pathogens. We used a non-human primate model of simian immunodeficiency virus (SIV)-Mtb co-infection, in which latent Mtb infection was established prior to SIVmac251 infection. The evolutionary dynamics of SIV env was evaluated from samples in plasma, lymph nodes, and lungs (including granulomas) of SIV-Mtb co-infected and SIV only control animals. While the diversity of the challenge virus was low and overall viral diversity remained relatively low over 6–9 weeks, changes in viral diversity and divergence were observed, including evidence for tissue compartmentalization. Overall, viral diversity was highest in SIV-Mtb animals that did not develop clinical Mtb reactivation compared to animals with Mtb reactivation. Among lung granulomas, viral diversity was positively correlated with the frequency of CD4+ T cells and negatively correlated with the frequency of CD8+ T cells. SIV diversity was highest in the thoracic lymph nodes compared to other sites, suggesting that lymphatic drainage from the lungs in co-infected animals provides an advantageous environment for SIV replication. This is the first assessment of SIV diversity across tissue compartments during SIV-Mtb co-infection after established Mtb latency.

Highlights

38 million people worldwide are infected with human immunodeficiency virus (HIV) and they are 20 times more likely to become ill with tuberculosis (TB) than uninfected individuals [1]
HIV-TB co-infection in humans is associated with increased HIV-1 replication and diversity, though the mechanism is poorly understood
Our study assessed genetic diversity of simian immunodeficiency virus (SIV) in macaques infected with SIV only, or co-infected with Mycobacterium tuberculosis (Mtb)

Summary

Introduction

38 million people worldwide are infected with HIV and they are 20 times more likely to become ill with tuberculosis (TB) than uninfected individuals [1]. While the complex synergy between HIV and Mtb is not well understood, it is known that infection with one pathogen accelerates the progression of the other [2]. HIV progression is because HIV/Mtb co-infected individuals have higher viremia [3] and within-host HIV diversity in the plasma [4,5] compared to individuals infected with HIV only. HIV diversity in turn plays a key role in disease progression, as higher diversity can lead to the generation of mutants that result in viral immune escape and resistance to drugs. Higher plasma viremia and faster disease progression are known to be associated with higher viral diversity [6,7,8,9,10]. HIV is the most common risk factor to progression to active TB, which can occur after primary Mtb infection or long-standing controlled latent

Objectives

Results

Conclusion