Relationship between viral load in blood, cerebrospinal fluid, brain tissue and isolated microglia with neurological disease in macaques infected with different strains of SIV

Dynamics of Viral and Proviral Loads of FelineImmunodeficiency Virus within the Feline Central Nervous System duringthe Acute Phase following IntravenousInfection

“…In fact, at the last time point of the study, only one animal had no detectable virus within the CNS or CSF, which would be more suggestive of a lack of CNS infection than of a transient infection which had been cleared or reduced to undetectable concentrations. While studies using similar quantification techniques have been undertaken using the SIV model, such studies have been primarily concerned with viral loads as they related to the end stages of disease, when the animal is likely to have encephalitis (20,68). A recent study on an accelerated model of SIV-induced encephalitis revealed CNS viral loads in all animals at 10 weeks after infection, but in contrast to the present study, loads rapidly reduced to undetectable concentrations by 3 weeks, with a resurgence of loads in selected animals by 7 weeks (18).…”

“…The lesions of meningeal, choroid plexus, and parenchymal mononuclear cell perivascular cuffing observed in the acute phase of infection are essentially features of the trafficking of mononuclear cells through the CNS, and as documented previously (7,8,20,37), some of these cells are likely to be infected with virus. It is believed, however, that in HIV infection such cell accumulations are not due to localized virus production but are a reflection of a generalized systemic immune stimulation (29).…”

“…While many studies positively correlated viral loads with end-stage neuropathology in HIV, SIV, and FIV infections (7,20,29,63,68), the present study focused on the pathology associated with the acute phase of infection, and thus, there are few comparable studies (10,18,58). The lesions of meningeal, choroid plexus, and parenchymal mononuclear cell perivascular cuffing observed in the acute phase of infection are essentially features of the trafficking of mononuclear cells through the CNS, and as documented previously (7,8,20,37), some of these cells are likely to be infected with virus.…”

“…This technique is an improvement on previous quantitative or semiquantitative PCR-based methods. Studies correlating plasma, CSF, and brain viral and proviral loads have been documented to a limited degree for HIV and SIV infection and in particular have focused on asymptomatic or end stages of disease (20,63,68). More recently, evaluations of the acute phase of FIV and SIV infections have been reported (10,18).…”

Enhanced Expression of Proinflammatory Cytokines in the Central Nervous System Is Associated with Neuroinvasion by Simian Immunodeficiency Virus and the Development of Encephalitis

“…From this body of work, it has been well documented that viral neuroinvasion occurs early following SIV infection. Virus is routinely detected in the CNS by 7 to 14 days after infection (2,6,11,15,44). Neuroinvasion is correlated with increased numbers of perivascular macrophages, enhanced endothelial expression of vascular cell adhesion molecule 1 (VCAM-1), and evidence of intrathecal immune activation (12,15,25,32,44).…”