Inhibitory and Stimulatory Effects of IL-32 on HIV-1 Infection.

The proinflammatory cytokine IL-32 is elevated in the plasma and tissues of HIV-1-infected individuals. However, its significance in HIV-1 infection remains unclear because IL-32 inhibits and stimulates viral production in monocyte-derived macrophages (MDMs) and CD4+ T cells, respectively. In this study, we initially found that the inhibitory effect on human MDMs depends on SAMHD1, a dNTP triphosphohydrolase that inhibits viral reverse transcription. IL-32 increased the unphosphorylated active form of SAMHD1, which was consistent with the reduced expression of the upstream cyclin-dependent kinases. Indeed, IL-32 lost its anti-HIV-1 activity in MDMs when SAMHD1 was depleted. These results explain why IL-32 inhibits HIV-1 in MDMs but not CD4+ T cells, because SAMHD1 restricts HIV-1 in noncycling MDMs but not in cycling CD4+ T cells. Another unique feature of IL-32 is the induction of the immunosuppressive molecule IDO1, which is beneficial for HIV-1 infection. In this study, we found that IL-32 also upregulates other immunosuppressive molecules, including PD-L1, in MDMs. Moreover, IL-32 promoted the motility of MDMs, which potentially facilitates intercellular HIV-1 transmission. Our findings indicate that IL-32 has both the direct inhibitory effect on HIV-1 production in MDMs and the indirect stimulatory effects through phenotypic modulation of MDMs, and they suggest that the stimulatory effects may outweigh the inhibitory effect because the window for IL-32 to inhibit HIV-1 is relatively confined to SAMHD1-mediated reverse transcription suppression in the viral life cycle.

M-Sec induced by HTLV-1 mediates an efficient viral transmission.

Human T-cell leukemia virus type 1 (HTLV-1) infects target cells primarily through cell-to-cell routes. Here, we provide evidence that cellular protein M-Sec plays a critical role in this process. When purified and briefly cultured, CD4+ T cells of HTLV-1 carriers, but not of HTLV-1- individuals, expressed M-Sec. The viral protein Tax was revealed to mediate M-Sec induction. Knockdown or pharmacological inhibition of M-Sec reduced viral infection in multiple co-culture conditions. Furthermore, M-Sec knockdown reduced the number of proviral copies in the tissues of a mouse model of HTLV-1 infection. Phenotypically, M-Sec knockdown or inhibition reduced not only plasma membrane protrusions and migratory activity of cells, but also large clusters of Gag, a viral structural protein required for the formation of viral particles. Taken together, these results suggest that M-Sec induced by Tax mediates an efficient cell-to-cell viral infection, which is likely due to enhanced membrane protrusions, cell migration, and the clustering of Gag.

M-Sec facilitates intercellular transmission of HIV-1 through multiple mechanisms.

BACKGROUND: HIV-1 promotes the formation of tunneling nanotubes (TNTs) that connect distant cells, aiding cell-to-cell viral transmission between macrophages. Our recent study suggests that the cellular protein M-Sec plays a role in these processes. However, the timing, mechanism, and to what extent M-Sec contributes to HIV-1 transmission is not fully understood, and the lack of a cell line model that mimics macrophages has hindered in-depth analysis. RESULTS: We found that HIV-1 increased the number, length and thickness of TNTs in a manner dependent on its pathogenic protein Nef and M-Sec in U87 cells, as observed in macrophages. In addition, we found that M-Sec was required not only for TNT formation but also motility of U87 cells, both of which are beneficial for viral transmission. In fact, M-Sec knockdown in U87 cells led to a significantly delayed viral production in both cellular and extracellular fractions. This inhibition was observed for wild-type virus, but not for a mutant virus lacking Nef, which is known to promote not only TNT formation but also migration of infected macrophages. CONCLUSIONS: By taking advantage of useful features of U87 cells, we provided evidence that M-Sec mediates a rapid and efficient cell-cell transmission of HIV-1 at an early phase of infection by enhancing both TNT formation and cell motility.

Risk Factors Associated with Parasitic Infection Among Municipality Solid-Waste Workers in an Egyptian Community.

Solid-waste management is associated with several health hazards, particularly parasitic infection. The objective of the study was to determine the association between risk factors and the occurrence of intestinal parasitic infections (potentially pathogenic) among municipal waste collectors in Alexandria, Egypt. A cross-sectional survey was conducted in the main municipality company in Alexandria. A total of 346 municipality solid-waste workers (MSWWs) was interviewed using an in-depth questionnaire. The type of parasitic infections among waste handlers was determined using formol-ether concentration and modified Ziehl-Neelsen technique. About half of the workers were infected with parasites. The profile of parasitic infection revealed 12 parasitic species. These were comprised of the following helminths: Schistosoma mansoni (13.3%), Enterobius vermicularis (1.7%), Ascaris lumbricoides (1.4%), and Hymenolepis nana ova (0.6%). Among protozoa were pathogenic Entamoeba histolytica (3.2%), Giardia intestinalis (2.9%), nonpathogenic protozoa such as Entamoeba coli (1.7%), and potentially pathogenic or opportunistic ones as Cryptosporidium (23.4%), Microsporidia (20.25%), Cyclospora (2.0%), Blastocystis hominis (1.7%), and Cystoisospora belli (1.2%). About 1.4% of MSWWs have pediculosis and phthiriasis in their scalp and eyelashes respectively. Risk factors for infection were associated with direct exposure to solid fecal waste (odds ratio [OR] = 1.8, confidence interval [CI] = 1.1-3.0) and occupational activities that allowed for direct exposure to solid fecal waste (OR = 2.3, CI = 1.4-4.0). Logistic regression model has revealed that educational level and residence were the factors that contribute to parasitic infection among MSWWs (P < 0.05). MSWWs are at high risk of acquiring parasitic infections. Data of the present study highlighted the need for greater biomonitoring of MSWWs and the improvement of environmental conditions and health care in such marginalized communities to prevent parasitic infection and associated morbidities.

Adverse health problems among municipality workers in alexandria (egypt).

BACKGROUND: Solid waste management has emerged as an important human and environmental health issue. Municipal solid waste workers (MSWWs) are potentially exposed to a variety of occupational biohazards and safety risks. The aim of this study was to describe health practices and safety measures adopted by workers in the main municipal company in Alexandria (Egypt) as well as the pattern of the encountered work related ill health. METHODS: A cross-sectional study was conducted between January and April 2013. We interviewed and evaluated 346 workers serving in about 15 different solid waste management activities regarding personal hygiene, the practice of security and health care measures and the impact of solid waste management. RESULTS: Poor personal hygiene and self-care, inadequate protective and safety measures for potentially hazardous exposure were described. Impact of solid waste management on health of MSWWs entailed high prevalence of gastrointestinal, respiratory, skin and musculoskeletal morbidities. Occurrence of accidents and needle stick injuries amounted to 46.5% and 32.7% respectively. The risk of work related health disorders was notably higher among workers directly exposed to solid waste when compared by a group of low exposure potential particularly for diarrhea (odds ratio [OR] = 2.2, 95% confidence interval [CI] = 1.2-3.8), vomiting (OR = 2.7, 95% CI = 1.1-6.6), abdominal colic (OR = 1.9, 95% CI = 1.1-3.2), dysentery (OR = 3.6, 95% CI = 1.3-10), dyspepsia (OR = 1.8, 95% CI = 1.1-3), low back/sciatic pain (OR = 3.5, 95% CI = 1.8-7), tinnitus (OR = 6.2, 95% CI = 0.3-122) and needle stick injury (OR = 3.4, 95% CI = 2.1-5.5). CONCLUSIONS: Workers exposed to solid waste exhibit significant increase in risk of ill health. Physician role and health education could be the key to assure the MSWWs health safety.