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Nature microbiology 7(11), 1762 - 1776 (2022). doi:10.1038/s41564-022-01247-0, Of the 13 known independent zoonoses of simian immunodeficiency viruses to humans, only one, leading to human immunodeficiency virus (HIV) type 1(M) has become pandemic, causing over 80 million human infections. To understand the specific features associated with pandemic human-to-human HIV spread, we compared replication of HIV-1(M) with non-pandemic HIV-(O) and HIV-2 strains in myeloid cell models. We found that non-pandemic HIV lineages replicate less well than HIV-1(M) owing to activation of cGAS and TRIM5-mediated antiviral responses. We applied phylogenetic and X-ray crystallography structural analyses to identify differences between pandemic and non-pandemic HIV capsids. We found that genetic reversal of two specific amino acid adaptations in HIV-1(M) enables activation of TRIM5, cGAS and innate immune responses. We propose a model in which the parental lineage of pandemic HIV-1(M) evolved a capsid that prevents cGAS and TRIM5 triggering, thereby allowing silent replication in myeloid cells. We hypothesize that this capsid adaptation promotes human-to-human spread through avoidance of innate immune response activation., Published by Nature Publishing Group, London

The type one interferon induced restriction factor Myxovirus resistance B (MxB) restricts HIV-1 nuclear entry evidenced by inhibition of 2-LTR but not linear forms of viral DNA. The HIV-1 capsid is the key determinant of MxB sensitivity and cofactor binding defective HIV-1 capsid mutants P90A (defective for cyclophilin A and Nup358 recruitment) and N74D (defective for CPSF6 recruitment) have reduced dependency on nuclear transport associated cofactors, altered integration targeting preferences and are not restricted by MxB expression. This has suggested that nuclear import mechanism may determine MxB sensitivity. Here we have use genetics to separate HIV-1 nuclear import cofactor dependence from MxB sensitivity. We provide evidence that MxB sensitivity depends on HIV-1 capsid conformation, rather than cofactor recruitment. We show that depleting CPSF6 to change nuclear import pathway does not impact MxB sensitivity, but mutants that recapitulate the effect of Cyclophilin A binding on capsid conformation and dynamics strongly impact MxB sensitivity. We demonstrate that HIV-1 primary isolates have different MxB sensitivities due to cytotoxic T lymphocyte (CTL) selected differences in Gag sequence but similar cofactor dependencies. Overall our work demonstrates a complex relationship between cyclophilin dependence and MxB sensitivity likely driven by CTL escape. We propose that cyclophilin binding provides conformational flexibility to HIV-1 capsid facilitating simultaneous evasion of capsid-targeting restriction factors including TRIM5 as well as MxB.

Objective: Securing the airway of a wounded soldier while operating in a light-restricted combat environment may be required of forward-deployed military medical personnel. The best method of obtaining such an airway has not been addressed. In this pilot study, the objective was to examine the use of endotracheal intubation using an infrared filtered laryngoscope and night vision goggles. Methods: The investigators performed endotracheal intubation, using an infrared filter light source laryngoscope, on patients undergoing elective surgical procedures. All intubations took place in a completely darkened operating room. Results: Twenty-one patients (91.3%) were intubated successfully as defined in the study. No adverse outcomes or complications occurred. Conclusions: This study demonstrates that endotracheal intubation can be performed using a laryngoscope with an infrared filter and night vision goggles with a high success rate in a select population in a darkened environment.

The intrasulcular incision provides excellent transpalatine exposure of the nasopharynx with a viable palatal flap. There is less chance for naso-oral fistula formation since the resulting suture line is always over underlying bone. This safely allows extensive removal of the hard palate. Additionally, the continuous sling suture allows excellent flap reapproximation using the teeth as anchors for the replaced palatal flap. Patients tolerate oral feedings within 24 hours of their operations and require minimal postoperative analgesics. The extended intrasulcular incision offers many advantages over other methods for transpalatine exposures to the nasopharynx.

The report of case presents the postnatal and early infancy period for a child born with a cleft of the soft palate. The infant was admitted to the hospital several times for failure to thrive as a result of feeding difficulties. The feeding problems resulted from both the cleft and a lack of consistent and concerted effort by the family to nourish the infant. When the child was 3 months old, a feeding obturator was constructed that resulted in improvement in the child's weight gain. The feeding problems of an infant with a cleft palate and the pressures that these problems present to the parents are discussed.

SUMMARYPandemic viruses remain a global threat to health and economics but how they adapt to become pandemic remains poorly understood. Here we compare pandemic HIV-1(M) and non-pandemic HIV-(O) and HIV-2 strains finding that non-pandemic HIV replicate poorly in myeloid cell models due to activation of cGAS and TRIM5, and ensuing antiviral responses. We use phylogenetics and viral capsid structural biology to define specific differences between pandemic and non-pandemic HIV capsids and demonstrate that their genetic reversal in HIV-1(M) mutants causes TRIM5, cGAS and innate immune activation. We propose a model in which the parental lineage of pandemic HIV-1(M) has uniquely evolved a dynamic capsid that avoids activation of cGAS and TRIM5 to establish cloaked replication in myeloid cells. The unique adaptations of the pandemic virus lineage suggests a role in effective human-to-human transmissibility and highlight the importance of avoiding innate immune activation during pandemic human-to-human viral transmission.