Recombinant HIV type 1 gp140 (group M, CRF07_BC) [His]

Background: Understanding geographic patterns of HIV transmission is critical to designing effective interventions. We characterized geographic proximity by transmission risk and urban-rural characteristics among people with closely related HIV strains suggestive of potential transmission relationships. Methods: We analyzed US National HIV Surveillance System data of people diagnosed between 2010 and 2016 with a reported HIV-1 partial polymerase nucleotide sequence. We used HIV TRAnsmission Cluster Engine (HIV-TRACE) to identify sequences linked at a genetic distance of <= 0.5%. For each linked person, we assessed median distances between counties of residence at diagnosis by transmission category and urban-rural classification, weighting observations to account for persons with multiple linked sequences. Results: There were 24,743 persons with viral sequence linkages to at least one other person included in this analysis. Overall, half (50.9%) of persons with linked viral sequences resided in different counties, and the median distance from persons with linked viruses was 11 km/7 miles [interquartile range (IQR), 0-145 km/90 miles]. Median distances were highest for men who have sex with men (MSM: 14 km/9 miles; IQR, 0-179 km/111 miles) and MSM who inject drugs, and median distances increased with increasing rurality (large central metro: 0 km/miles; IQR, 0-83 km/52 miles; nonmetro: 103 km/64 miles; IQR, 40 km/25 miles-316 km/196 miles). Conclusion: Transmission networks in the United States involving MSM, MSM who inject drugs, or persons living in small metro and nonmetro counties may be more geographically dispersed, highlighting the importance of coordinated health department efforts for comprehensive follow-up and linkage to care.

Background Osteopontin (OPN) as a secreted signaling protein is dramatically induced in response to cellular injury and neurodegeneration. Microglial inflammatory responses in the brain are tightly associated with the neuropathologic hallmarks of neurodegenerative disease, but understanding of the molecular mechanisms remains in several contexts poorly understood. Methods Micro-positron emission tomography (PET) neuroimaging using radioligands to detect increased expression of the translocator protein (TSPO) receptor in the brain is a non-invasive tool used to track neuroinflammation in living mammals. Results In humanized, chronically HIV-infected female mice in which OPN expression was knocked down with functional aptamers, uptake of TSPO radioligand DPA-713 was markedly upregulated in the cortex, olfactory bulb, basal forebrain, hypothalamus, and central grey matter compared to controls. Microglia immunoreactive for Iba-1 were more abundant in some HIV-infected mice, but overall, the differences were not significant between groups. TSPO(+)microglia were readily detected by immunolabeling of post-mortem brain tissue and unexpectedly, two types of neurons also selectively stained positive for TSPO. The reactive cells were the specialized neurons of the cerebellum, Purkinje cells, and a subset of tyrosine hydroxylase-positive neurons of the substantia nigra. Conclusions In female mice with wild-type levels of osteopontin, increased levels of TSPO ligand uptake in the brain was seen in animals with the highest levels of persistent HIV replication. In contrast, in mice with lower levels of osteopontin, the highest levels of TSPO uptake was seen, in mice with relatively low levels of persistent infection. These findings suggest that osteopontin may act as a molecular brake regulating in the brain, the inflammatory response to HIV infection.