No abstract

Healthcare resource availability is potentially associated with COVID-19 mortality, and the potentially uneven geographical distribution of resources is a looming concern in the global pandemic. Given that access to healthcare resources is important to overall population health, assessing COVID-19 patients' access to healthcare resources is needed. This paper aims to examine the temporal variations in the spatial accessibility of U.S. COVID-19 patients to medical facilities, identify areas that are likely to be overwhelmed by the COVID-19 pandemic, and explore associations of low access areas with their socioeconomic and demographic characteristics. We use a three-step floating catchment area method, spatial statistics, and logistic regression to achieve the goals. Findings of this research in the State of Florida revealed that North Florida, rural areas, and zip codes with more Latino or Hispanic populations are more likely to have lower access than other regions during the COVID-19 pandemic. Our approach can help policymakers identify potentially possible low access areas and establish appropriate policy intervention paying attention to those areas during a pandemic.

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The capsid (CA) protein lattice of HIV-1 and other retroviruses encases viral 1 genomic RNA and regulates steps that are essential to retroviral invasion of 2 target cells, including reverse transcription, nuclear trafficking, and integration of 3 viral cDNA into host chromosomal DNA 1 . Cyclophilin A (CypA), the first cellular 4 protein reported to bind HIV-1 CA 2 , has interacted with invading lentiviruses 5 related to HIV-1 for millions of years 3-7 . Disruption of the CA-CypA interaction 6 decreases HIV-1 infectivity in human cells 8-12 , but stimulates infectivity in non-7 human primate cells 13-15 . Genetic and biochemical data suggest that CypA 8 interaction with CA protects HIV-1 from a restriction factor in human cells 16-20 . 9 Discovery of the CA-specific restriction factor TRIM5α 21 , and of TRIM5-CypA 10 fusion genes that were independently generated at least four times in 11 phylogeny 4,5,15,22-25 , pointed to human TRIM5α as the CypA-sensitive restriction 12 factor. However, significant HIV-1 restriction by human TRIM5α 21 , let alone 13 inhibition of such activity by CypA 26 , has not been detected. Here, exploiting 14 reverse genetic tools optimized for primary human CD4 + T cells, macrophages, 15 and dendritic cells, we demonstrate that disruption of the CA-CypA interaction 16 renders HIV-1 susceptible to restriction by human TRIM5α, with the block 17 occurring before reverse transcription. Identical findings were obtained with 18 single-cycle vectors or with replication-competent HIV-1, including sexually-19 transmitted clones from sub-Saharan Africa. Endogenous TRIM5α was observed 20 to associate with virion cores as they entered the macrophage cytoplasm, but 21 only when the CA-CypA interaction was disrupted. These experiments resolve the 22 long-standing mystery of the role of CypA in HIV-1 replication by demonstrating 23 that this ubiquitous cellular protein shields HIV-1 from previously inapparent, but 24 potent inhibition, imposed by human TRIM5α. Hopefully this reinvigorates 25 development of CypA-inhibitors for treatment of HIV-1 and other CypA-dependent 26 pathogens 27-30 . 27To assess the role of TRIM5α and CypA in the primary human blood cell types 1 that serve as targets for HIV-1 infection in vivo, lentiviral vectors were optimized for titer 2 and knockdown efficiency in these cells 26,[31][32][33][34] . Human macrophages, dendritic cells, 3 and CD4 + T cells were transduced with lentivectors bearing a puromycin resistance 4 cassette and shRNAs targeting either TRIM5 or luciferase (Luc) as a control. After three 5 days of selection in puromycin, knockdown was confirmed by RT-qPCR for TRIM5 6 mRNA, and by rescue of N-MLV restriction (Extended Data Fig. 2a-c), as done 7 previously 26,31 . TRIM5 and Luc control knockdown cells were then challenged with 8 single-cycle, VSV G-pseudotyped, HIV-1-GFP reporter vectors. Three days later, the 9 percentage of GFP + cells was assessed by flow cytometry as a measure of infectivity 10

No abstract

These results indicate that Rev-dependent, intron-containing, HIV-1 RNA is detected by the innate immune system, and that drugs which inhibit HIV-1 transcription or Revdependent, HIV-1 RNA metabolism, would add qualitative benefit to current antiviral drug regimens.

33Tripartite motif-containing protein 5a (TRIM5a) functions as a cellular antiviral restriction 34 factor with exquisite specificity towards the capsid lattices of retroviruses. The relative avidity 35 of TRIM5a binding to retrovirus capsids directly impacts primate species susceptibility to 36 infection, but the antiviral role of TRIM5a is thought limited to retroviruses. In contrast to this 37 current understanding, here we show that both human and rhesus TRIM5a possess potent 38 antiviral function against specific flaviviruses through interaction with the viral protease 39 (NS2B/3) to inhibit virus replication. Importantly, TRIM5a was essential for the antiviral 40 function of IFN-I against sensitive flaviviruses in human cells. However, TRIM5a was ineffective 41 against mosquito-borne flaviviruses (yellow fever, dengue, and Zika viruses) that establish 42 transmission cycles in humans following emergence from non-human primates. Thus, TRIM5a 43 is revealed to possess remarkable plasticity in recognition of diverse virus families, with 44 potential to influence human susceptibility to emerging flaviviruses of global concern. 45 46 47 Main 48Flaviviruses (family Flaviviridae) include 53 recognized virus species of which 40 are known to 49 cause disease in humans, with over 40% of the world's population at risk of flavivirus infection 50 annually 1 . These viruses have high potential for emergence into human populations as 51 witnessed historically through global emergence of dengue virus (DENV), West Nile virus 52 (WNV), and Zika virus (ZIKV). Additional (re)emerging viruses of considerable medical 53 importance include yellow fever virus (YFV), Japanese encephalitis virus (JEV) and members of 54 the tick-borne encephalitis virus (TBEV) serogroup. Flaviviruses share in common a positive-55 sense single-stranded RNA (ssRNA) genome encoding a single polyprotein that is cleaved by 56 host cell signalases 2 and the viral protease to generate three structural (capsid [C], pre-57 membrane [M] and envelope [E]) and seven nonstructural (NS) proteins (NS1, NS2A, NS2B, NS3, 58NS4A, NS4B and NS5) 3 . Two of the nonstructural proteins have enzymatic activity; the NS3 59 protein encodes the viral RNA helicase and together with its co-factor NS2B (NS2B/3) functions 60

Cooling centers have played a significant role in reducing the risks of adverse health impacts of extreme heat exposure. However, there have been no comparative studies investigating cooling center preparedness in terms of population coverage, location efficiency, and population coverage disparities among different subpopulation groups. Using a catchment area method with a 0.8 km walking distance, we compared three aspects of cooling center preparedness across twenty-five cities in the U.S. We first calculated the percentage of the population covered by a single cooling center for each city. Then, the extracted values were separately compared to the city’s heat indexes, latitudes, and spatial patterns of cooling centers. Finally, we investigated population coverage disparities among multiple demographics (age, race/ethnicity) and socioeconomic (insurance, poverty) subpopulation groups by comparing the percentage of population coverage between selected subpopulation groups and reference subpopulation groups. Our results showed that cooler cities, higher latitude cities, and cities with dispersed cooling centers tend to be more prepared than warmer cities, lower latitude cities, and cities with clustered cooling centers across the U.S. Moreover, older people (≥65) had 9% lower population coverage than younger people (≤64). Our results suggest that the placement of future cooling centers should consider both the location of other nearby cooling centers and the spatial distribution of subpopulations to maximize population coverage and reduce access disparities among several subpopulations.