HIV-1 interacts with human endogenous retrovirus K (HML-2) envelopes derived from human primary lymphocytes.

UNLABELLED: Human endogenous retroviruses (HERVs) are viruses that have colonized the germ line and spread through vertical passage. Only the more recently acquired HERVs, such as the HERV-K (HML-2) group, maintain coding open reading frames. Expression of HERV-Ks has been linked to different pathological conditions, including HIV infection, but our knowledge on which specific HERV-Ks are expressed in primary lymphocytes currently is very limited. To identify the most expressed HERV-Ks in an unbiased manner, we analyzed their expression patterns in peripheral blood lymphocytes using Pacific Biosciences (PacBio) single-molecule real-time (SMRT) sequencing. We observe that three HERV-Ks (KII, K102, and K18) constitute over 90% of the total HERV-K expression in primary human lymphocytes of five different donors. We also show experimentally that two of these HERV-K env sequences (K18 and K102) retain their ability to produce full-length and posttranslationally processed envelope proteins in cell culture. We show that HERV-K18 Env can be incorporated into HIV-1 but not simian immunodeficiency virus (SIV) particles. Moreover, HERV-K18 Env incorporation into HIV-1 virions is dependent on HIV-1 matrix. Taken together, we generated high-resolution HERV-K expression profiles specific for activated human lymphocytes. We found that one of the most abundantly expressed HERV-K envelopes not only makes a full-length protein but also specifically interacts with HIV-1. Our findings raise the possibility that these endogenous retroviral Env proteins could directly influence HIV-1 replication. IMPORTANCE: Here, we report the HERV-K expression profile of primary lymphocytes from 5 different healthy donors. We used a novel deep-sequencing technology (PacBio SMRT) that produces the long reads necessary to discriminate the complexity of HERV-K expression. We find that primary lymphocytes express up to 32 different HERV-K envelopes, and that at least two of the most expressed Env proteins retain their ability to make a protein. Importantly, one of them, the envelope glycoprotein of HERV-K18, is incorporated into HIV-1 in an HIV matrix-specific fashion. The ramifications of such interactions are discussed, as the possibility of HIV-1 target tissue broadening and immune evasion are considered.

Ileal conduit to small intestine fistula following extensive abdominopelvic resection and radiation for metastatic colon cancer.

A woman in her mid-60s presented with decreased output from urostomy, which was an opening from the neobladder (ileal conduit). Presentation was preceded by a 6-month history of alternating faecaluria and increased colostomy output. Laboratory studies were notable for normal anion gap metabolic acidosis. Creatinine level of the colostomy output was 17.7 mg/dL, a finding indicative of the presence of urine in the sample. CT enterography and X-ray loopogram confirmed neobladder to small intestine fistula.Neobladder creation is commonly performed in patients with bladder cancer requiring resection. Fistulas between the neobladder and intestine are observed in fewer than 2.7% of cases. The patient's history of extensive abdominopelvic resection, colostomy creation and radiation likely contributed to fistula development. We highlight the need for a high index of suspicion for a fistula in a patient with a neobladder experiencing recurrent urinary tract infections or a high colostomy output concurrently with low neobladder output.

A Review of Treatment-Induced Pulmonary Toxicity in Breast Cancer.

This article reviews the available literature that describes the incidence, diagnosis, mechanism, symptoms, and management of pulmonary toxicity induced by radiation therapy and current systemic medications used to treat breast cancer. An extensive literature search was conducted via Ovid Medline to identify all potentially relevant articles written in English from 2010 through January 2020. Additional relevant articles outside the time frame were included as needed. Although the risk of pulmonary toxicity from various breast cancer treatments is small in most instances, it can be fatal. Due to the high prevalence of breast cancer and the range of treatment options, healthcare providers should be aware of the risk of pulmonary toxicity from those treatments and how to prevent or manage complications.

Association of premature atherosclerotic cardiovascular disease with higher risk of cancer: a behavioral risk factor surveillance system study.

AIM: The aim of this study was to investigate a possible association between atherosclerotic cardiovascular disease (ASCVD) and risk of cancer in young adults. METHODS: We utilized data from the Behavioral Risk Factor Surveillance System, a nationally representative US telephone-based survey to identify participants in the age group of 18-55 years who reported a history of ASCVD. These patients were defined as having premature ASCVD. Weighted multivariable logistic regression models were used to study the association between premature ASCVD and cancer including various cancer subtypes. RESULTS: Between 2016 and 2019, we identified 28 522 (3.3%) participants with a history of premature ASCVD. Compared with patients without premature ASCVD, individuals with premature ASCVD were more likely to be Black adults, have lower income, lower levels of education, reside in states without Medicaid expansion, have hypertension, diabetes mellitus, chronic kidney disease, obesity, and had delays in seeking medical care. Individuals with premature ASCVD were more likely to have been diagnosed with any form of cancer (13.7% vs 3.9%), and this association remained consistent in multivariable models (odds ratio, 95% confidence interval: 2.08 [1.72-2.50], P < 0.01); this association was significant for head and neck (21.08[4.86-91.43], P < 0.01), genitourinary (18.64 [3.69-94.24], P < 0.01), and breast cancer (3.96 [1.51-10.35], P < 0.01). Furthermore, this association was consistent when results were stratified based on gender and race, and in sensitivity analysis using propensity score matching. CONCLUSION: Premature ASCVD is associated with a higher risk of cancer. These data have important implications for the design of strategies to prevent ASCVD and cancer in young adults.

Expression of HERV-K108 envelope interferes with HIV-1 production.

The human endogenous retroviruses (HERV)-K of the HML-2 group include full-length or near full-length elements encoding functional proteins, and are classified as type-1 or type-2 (type-1 has a deletion in the 5' end of the env gene). Because proteins of different retroviruses can interact, we hypothesized that HERV-K envelope (Env) could influence HIV-1 replication. Here we describe the negative effect of envelope expression of certain type-2 HERV-Ks on HIV-1 production. All HIV-1 and SIV strains tested were susceptible to various degrees to inhibition by the HERV-K108 envelope. We identified four residues within HERV-K108 Env as being critical to inhibit HIV-1 production. No inhibition was observed on EGFP expression, indicating that HERV-K Env does not affect general protein production. These findings demonstrate that envelope proteins from some endogenous retroviruses can limit production of exogenous lentiviruses such as HIV-1. Future studies will elucidate the mechanism mediating HIV-1 inhibition by HERV Envs.