Intracellular defense proteins, also referred to as restriction factors, are capable of interfering with different steps of the viral life cycle. Among these, we have shown that Tripartite motif 22 (TRIM22) suppresses basal as well as phorbol ester-induced HIV-1 long terminal repeat (LTR)-mediated transcription, independently of its E3 ubiquitin ligase activity, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) binding to the U3 region and Tat interaction with the TAR region of the HIV-1 LTR. As basal HIV-1 transcription is driven by the transcription factor specificity protein 1 (Sp1), we have investigated whether TRIM22 could interfere with Sp1-driven transcriptional activation of the HIV-1 LTR. 293T cells, devoid of endogenous TRIM22 expression, were transfected with a TRIM22-expressing plasmid together with reporter plasmids driven by the HIV-1 LTR promoter either containing or lacking Sp1 binding sites or with reporter plasmids driven by non-viral promoter sequences either containing or lacking the three Sp1 binding sites from the HIV-1 LTR. These reporter assays showed that TRIM22 efficiently inhibited Sp1-driven transcription. Knocking down TRIM22 expression in the CD4+ SupT1 T cell line increased the replication of Sp1-dependent HIV-1 variants. TRIM22 did not interact with Sp1, but prevented binding of Sp1 to the HIV-1 promoter, as demonstrated in protein-DNA pull down and chromatin immunoprecipitation assays. TRIM22 acts as a suppressor of basal HIV-1 LTR-driven transcription by preventing Sp1 binding to the HIV-1 promoter.

Zika virus (ZIKV) is a recently re-emerged flavivirus transmitted to humans by mosquito bites but also from mother to fetus and by sexual intercourse. We here show that primary human endometrial stromal cells (HESC) are highly permissive to ZIKV infection and support its in vitro replication. ZIKV envelope expression was detected in the endoplasmic reticulum whereas double-stranded viral RNA colocalized with vimentin filaments to the perinuclear region. ZIKV productive infection also occurred in the human T-HESC cell line together with the induction of interferon-β (IFN-β) and of IFN-stimulated genes. Notably, in vitro decidualization of T-HESC with cyclic AMP and progesterone upregulated the cell surface expression of the ZIKV entry co-receptor AXL and boosted ZIKV replication by ca. 100-fold. Thus, endometrial stromal cells, particularly if decidualized, likely represent a crucial cell target of ZIKV reaching them, either via the uterine vasculature in the viremic phase of the infection or by sexual viral transmission, and a potential source of virus spreading to placental trophoblasts during pregnancy.

Sarcopenia is a physiopathological process associated with aging, caused by reduction of muscle strength, muscle quality and physical performance, and associated with an increased risk of falls, physical disability and premature death. There is no effective treatment for sarcopenia, but physical exercise seems to be highly effective at counteracting the decline in muscle mass and strength associated with aging. Recently, sarcopenia has been recognized as an emerging issue in people living with HIV (PLWH). Despite adequate treatment with combination antiretroviral therapy (cART), PLWH may exhibit an early occurrence of some aging-related conditions, including sarcopenia, frailty and falls, and this is likely resulting from high rates of comorbidities, high-risk behaviours, chronic immune activation and cART-specific factors. In this review, we discuss the potential mechanisms and the clinical relevance of sarcopenia in PLWH, and present data from longitudinal studies of physical activity in this population. Despite none of these studies having specifically addressed the benefits of physical exercise on sarcopenia, there is evidence that exercise is effective to increase aerobic capacity and muscle strength, and to improve body composition and inflammatory outcomes in PLWH. Therefore, the expected benefits of physical exercise are likely to translate into a successful and specific intervention for prevention and treatment of sarcopenia in this population.

To characterize parapoxviruses causing severe disease in wild ruminants in Stelvio Park, Italy, we sequenced and compared the DNA of several isolates. Results demonstrated that the red deer isolates are closely related to the parapox of red deer in New Zealand virus.