Aged Chinese-origin rhesus macaques infected with SIV develop marked viremia in absence of clinical disease, inflammation or cognitive impairment

Stephanie J Bissel,Kate Gurnsey,Charles W Bradberry,Clayton A Wiley,Guoji Wang,Nicholas F Smith,Hank P Jedema

doi:10.1186/s12977-018-0400-y

Stephanie J Bissel, Kate Gurnsey + Show 5 more

Open Access

https://doi.org/10.1186/s12977-018-0400-y

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Abstract

BackgroundDamage to the central nervous system during HIV infection can lead to variable neurobehavioral dysfunction termed HIV-associated neurocognitive disorders (HAND). There is no clear consensus regarding the neuropathological or cellular basis of HAND. We sought to study the potential contribution of aging to the pathogenesis of HAND. Aged (range = 14.7–24.8 year) rhesus macaques of Chinese origin (RM-Ch) (n = 23) were trained to perform cognitive tasks. Macaques were then divided into four groups to assess the impact of SIVmac251 infection (n = 12) and combined antiretroviral therapy (CART) (5 infected; 5 mock-infected) on the execution of these tasks.ResultsAged SIV-infected RM-Ch demonstrated significant plasma viremia and modest CSF viral loads but showed few clinical signs, no elevations of systemic temperature, and no changes in activity levels, platelet counts or weight. Concentrations of biomarkers of acute and chronic inflammation such as soluble CD14, CXCL10, IL-6 and TNF-α are known to be elevated following SIV infection of young adult macaques of several species, but concentrations of these biomarkers did not shift after SIV infection in aged RM-Ch and remained similar to mock-infected macaques. Neither acute nor chronic SIV infection or CART had a significant impact on accuracy, speed or percent completion in a sensorimotor test.ConclusionsViremia in the absence of a chronic elevated inflammatory response seen in some aged RM-Ch is reminiscent of SIV infection in natural disease resistant hosts. The absence of cognitive impairment during SIV infection in aged RM-Ch might be in part attributed to diminishment of some facets of the immunological response. Additional study encompassing species and age differences is necessary to substantiate this hypothesis.

Highlights

Damage to the central nervous system during human immunodeficiency virus (HIV) infection can lead to variable neurobehavioral dysfunction termed HIV-associated neurocognitive disorders (HAND)
Using baseline measurements for the speeded motor task, four performance and aged-matched groups were established at the end of the training period (Table 1): simian immunodeficiency virus (SIV)-infected, no treatment; mock-infected, no treatment; mock-infected combined antiretroviral therapy (CART) treated; and SIV-infected, CART treated
We show that aged rhesus macaques of Chinese origin (RM-Ch) present with minimal clinical signs during SIV infection despite substantial viremia

Summary

Introduction

Damage to the central nervous system during HIV infection can lead to variable neurobehavioral dysfunction termed HIV-associated neurocognitive disorders (HAND). Other comorbidities and behavioral traits have been reported to be risk factors for HAND such as cardiovascular-related conditions [15, 16], obesity [17], diabetes [16, 17], hyperlipidemia [16], tobacco use [16], hepatitis C co-infection [18], alcohol and substance abuse [14, 19], education [20, 21], poverty [21], sleep disorders [14], and psychiatric comorbidities [14] Many of these conditions are typically associated with aging and contribute to the assumption that HIV-infected individuals undergo a premature aging process. Regardless, the risk of developing HAND is likely confounded by many of these variables and will be challenging to tease apart, especially with older age

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