Lentiviral infection induces expression of MMPs in primary macrophages. Previously, improved MMP expression has become demonstrated while in the cerebrospinal uid of AIDS pa tients with HAD. Given that macrophages and microglia will be the principal CNS cell types infected by lentiviruses, we investigated MMP expression in key human and feline macrophages following infection with CSF derived strains of HIV and FIV. JRCSF, an infectious molecular clone of HIV 1 derived from a patient with HAD, was identified to induce the expression of MMP two and 9 protein and mRNA amounts. Similarly, the neurovirulent FIV isolate, V1CSF, induced MMP 2 and 9 expression in key feline cultures. Additionally, MMP expression was elevated early following infection by both virus and enhanced with viral replication over a one week time course.
These ndings demonstrated that lentiviral strains connected to CNS infection induced concurrent increases in MMP professional tein and mRNA expression in macrophages and recommended a probable mechanism typical to the pathogenesis of HIV and FIV. Properties and replication of lentivirus envelope chimeras. Sequence diversity in lentiviral envelope genes continues to be shown to in uence the expression of likely neurotoxins. Comparison selleck chemical from the V1CSF and Petaluma envelope surface unit sequences uncovered diversity ranging from two to 10%, based to the individual domain, using the sequences span ning the C3 to V5 selleck inhibitor areas exhibiting the greatest diversity. To assess the position of envelope variability in MMP expres sion, an FIV chimera was constructed by cloning envelope sequences from V1CSF into a genetic background dependant on a molecular clone on the much less neuro virulent FIV strain, Petaluma.
The FIV chimera was discovered to replicate in feline PBMC as ef ciently because the V1CSF and Petaluma mother or father viruses, but contrary to the infec tious 34TF10 clone, neither the chimera nor V1CSF replicated in CrFK cells. Similarly, we investigated

HIV chimeras that contained envelope sequences derived in the brains of demented and nondemented HIV infected individuals inside a T cell tropic HIV one molecular clone background. These clones, which had been previously proven to be macrophage tropic, differ from the extent to which they induced neuronal injury and possess envelope sequence diversity analogous to that observed be tween V1CSF and Petaluma. Both HAD and HIV ND chimeras replicated with equal ef ciency in main human PBMC cultures. MMP and STAT/JAK protein expression is improved fol lowing infection with lentiviruses expressing envelope se quences connected with neurological condition. To find out if sequence diversity in the lentivirus envelope gene could ac count for that variations observed in host cell gene expression, human and feline macrophages were infected together with the HIV and FIV envelope chimeras.