With a small genome of ~9.2 kb that encodes 14 major proteins, HIV must hijack host cellular machinery to successfully establish infection. These host proteins necessary for HIV replication are called “dependency factors.” Whole-genome, and then targeted screens were done to try to comprehensively identify all dependency factors acting throughout the HIV replication cycle.
Recent thymic emigrants that fail postpositive selection maturation are targeted by complement proteins. T cells likely acquire complement resistance during maturation in the thymus, a complement-privileged organ. To test this, thymocytes and fresh serum were separately obtained and incubated together in vitro to assess complement deposition. Complement binding decreased with development and maturation. Complement binding decreased from the double-positive thymocyte to the single-positive stage, and within single-positive thymocytes, complement binding gradually decreased with increasing intrathymic maturation. Binding of the central complement protein C3 to wild-type immature thymocytes required the lectin but not the classical pathway. Specifically, MBL2 but not MBL1 was required, demonstrating a unique function for MBL2. Previous studies demonstrated that the loss of NKAP, a transcriptional regulator of T cell maturation, caused peripheral T cell lymphopenia and enhanced complement susceptibility. To determine whether complement causes NKAP-deficient T cell disappearance, both the lectin and classical pathways were genetically ablated. This blocked C3 deposition on NKAP-deficient T cells but failed to restore normal cellularity, indicating that complement contributes to clearance but is not the primary cause of peripheral T cell lymphopenia. Rather, the accumulation of lipid peroxides in NKAP-deficient T cells was observed. Lipid peroxidation is a salient feature of ferroptosis, an iron-dependent nonapoptotic cell death. Thus, wild-type thymocytes naturally acquire the ability to protect themselves from complement targeting by MBL2 with maturation. However, NKAP-deficient immature peripheral T cells remain scarce in complement-deficient mice likely due to ferroptosis.
Background The annual reappearance of respiratory viruses has been recognized for decades. COVID‐19 mitigation measures taken during the pandemic were targeted at respiratory transmission and broadly impacted the burden of acute respiratory illnesses (ARIs). Methods We used the longitudinal Household Influenza Vaccine Evaluation (HIVE) cohort in southeast Michigan to characterize the circulation of respiratory viruses from March 1, 2020, to June 30, 2021, using RT‐PCR of respiratory specimens collected at illness onset. Participants were surveyed twice during the study period, and SARS‐CoV‐2 antibodies were measured in serum by electrochemiluminescence immunoassay. Incidence rates of ARI reports and virus detections were compared between the study period and a preceding pre‐pandemic period of similar duration. Results Overall, 437 participants reported a total of 772 ARIs; 42.6% had respiratory viruses detected. Rhinoviruses were the most frequent virus, but seasonal coronaviruses, excluding SARS‐CoV‐2, were also common. Illness reports and percent positivity were lowest from May to August 2020, when mitigation measures were most stringent. Seropositivity for SARS‐CoV‐2 was 5.3% in summer 2020 and increased to 11.3% in spring 2021. The incidence rate of total reported ARIs for the study period was 50% lower (95% CI: 0.5, 0.6; p < 0.001) than the incidence rate from a pre‐pandemic comparison period (March 1, 2016, to June 30, 2017). Conclusions The burden of ARI in the HIVE cohort during the COVID‐19 pandemic fluctuated, with declines occurring concurrently with the widespread use of public health measures. Rhinovirus and seasonal coronaviruses continued to circulate even when influenza and SARS‐CoV‐2 circulation was low.
Older adults hospitalized with severe COVID-19 are at higher risk of experiencing serious in-hospital outcomes and long-term health consequences following discharge. Declines in health and functional ability post-hospitalization are important infection-related outcomes. This study’s aim was to examine functional recovery one year following COVID-19 hospitalization. Twenty-one adults ≥60 years of age hospitalized with confirmed COVID-19 infection between 3/2020–5/2020 in Southeast Michigan completed a survey 9–15 months post-discharge including items from the Fried Frailty score, Short Form 36 Physical Assessment, PROMIS Dyspnea Scale, and the World Health Organization Disability Assessment Schedule. Mean age at hospital admission was 69 (standard deviation 7). Half of participants (52%) indicated they had too little energy to do the things they wanted to do, 52% (n=11) indicated moderate to severe shortness of breath when walking up two flights of stairs, and 43% (n=9) indicated they were limited a lot in walking several blocks. Additionally, 57% (n=12) indicated they were severely or extremely emotionally affected by their health due to their COVID-19 infection. Results were similar in only those ≥70 years (n=7). Our survey indicates that half of patients hospitalized with severe COVID-19 from the first infection wave in Southeast Michigan are significantly affected up to a year or more after their initial infection, and may benefit from long-term outpatient care. More research is needed to inform development of effective treatments for the long-term emotional and physical impacts of severe COVID-19.
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