The association of Chlamydia trachomatis and human papillomavirus co-infection with abnormal cervical cytology among women in south of Morocco.

PURPOSE: Evidence indicates that human papillomavirus (HPV) and Chlamydia trachomatis (CT) co-infection increases the risk of developing cervical pathogenesis. This study aims to assess the prevalence and possible risk factors of CT and HPV/CT co-infection in women from South of Morocco with normal and abnormal cytology. METHODS: Participants were recruited after signing an informed consent. Cervical samples were collected and analysed for the presence of HPV or CT. Detection of genomic DNA of both pathogens was performed by nested polymerase chain reaction. HPV genotypes defined by Sanger sequencing method. The association between demographic features and co-infection status was determined using a logistic regression model. A possible association between the presence of HPV and CT and cytological abnormality patterns was also investigated. RESULTS: We recruited n = 438 women, aged between 18 and 86 years. Around 59% of participants underwent a pap smear test for the first-time. Genomic DNA of HPV, CT and HPV/CT co-infection was detected in 32.3%, 17.7%, and 13.4% of the total samples, respectively. The identified risk factors associated with CT infection were history of sexually transmitted infections and marital status. By contrast, only smoking was found to be associated with HPV/CT co-infection. Evidence showed that co-infection was associated with an increased risk of developing cervical abnormalities (OR 3.18, 95% CI 0.96-9.21; p = 0.040). CONCLUSION: HPV and CT rates were high among the studied population. Evidence suggests that HPV/CT co-infected women were more susceptible to developing abnormal cytology.

Human Papillomavirus genotypes distribution and associated risk factors among women living in Southern Morocco.

Purpose: The aim of this work was to investigate potential risk factors associated with HPV infection and to determine the HPV genotype prevalence among women from the Southerns areas of Morocco. Methods: A total of n = 308 sexually active women provided their written consent to participate in this study. A detailed questionnaire was used to collect data, related to the age and life style of participants. HPV L1 gene detection was performed by a nested PCR method using consensus primers. HPV genotypes were determined using direct Sanger sequencing method. Statistical analysis of the results obtained was carried out using R software. Results: We detected HPV in 42.5 % of the total investigated samples. HPV infection was significantly associated with the following risk factors: age of the first intercourse (OR = 2.27, 95 % CI: 1.03-5.10, p = 0.044), and previous history of STIs (OR = 3.13, 95 % CI: 1.12-9.63, p = 0.034). High risk-HPV and Low risk-HPV genotypes were found in 26.6 % and 5.5 % of the participants, respectively. The most prevalent genotypes were HPV16 (22 %), HPV18 (2.6 %), HPV11 (1.6 %) and HPV83 (1.3 %). Multiple infections were found in 3.2 %. The genotypes covered by the bivalent, quadrivalent and nonavalent HPV vaccines account for 57.5 %, 62.8 % and 66.6 %, respectively. Conclusion: HPV infection prevalence reported in this study among women from the Southerns areas of Morocco is one of the highest reported in the country so far. Our finding confirm that the current HPV vaccines directed against the most prevalent HPV16 genotype, recently introduced in the country, should offer a good protection to the most vulnerable population if implemented properly. These results highlight the importance of HPV screening and vaccination programs in this region.

Awareness and knowledge associated to Human papillomavirus infection among university students in Morocco: A cross-sectional study.

Worldwide, cervical cancer is a real health issue, however, gaps exist in the public's awareness of the causal role of Human papillomavirus (HPV) in the development of this disease. This study aims to determine the level of awareness, knowledge and the associated factors on HPV among university students in Morocco. A cross-sectional study was conducted with a descriptive and analytical aim, among students attending Ibn Zohr University, in Agadir, Morocco. An interview questionnaire was used to collect information about the participants: demographic data, awareness and level of knowledge on HPV infection, and awareness of cervical cancer. Logistic regression analyses were used to determine the associated factors with awareness and level of knowledge on HPV. A total of 479 students participated in this study (mean age 21.82 ± 2.091). Most participants n = 391 (81.6%) were aware of cervical cancer, while only n = 7 (1.5%) identified HPV as a sexually transmitted infection. Among students, 10.0% (n = 48) were aware of HPV but only half of them n = 23 (47.9%) confirmed that HPV is associated with cervical cancer, and n = 29 (60.4%) showed low knowledge on HPV. Multivariate analysis revealed that HPV awareness has a strong association with a higher level of education (OR 4.04; 95% CI: 1.92-8.52), and with being a biology student (OR 5.20; 95% CI: 2.12-12.73), while high HPV knowledge was only associated with the female gender (OR 3.76; 95% CI: 1.01-13.92). The data suggest that university students in Morocco did not show sufficient knowledge of HPV infection and its consequences. This supports that earlier incorporation of sexual health education programs, especially related to HPV and cervical cancer, must be implemented in the university to reduce the burden of HPV-associated diseases among the population at risk.

HTLV-1-Tax and ICAM-1 act on T-cell signal pathways to polarize the microtubule-organizing center at the virological synapse.

Human T-lymphotropic virus type 1 (HTLV-1) spreads directly between lymphocytes and other cells via a specialized cell-cell contact, termed the virological synapse. The formation of the virological synapse is accompanied by the orientation of the microtubule-organizing center (MTOC) in the infected T cell toward the cell contact region with the noninfected target cell. We previously demonstrated that the combination of intracellular Tax protein expression and the stimulation of the intercellular adhesion molecule-1 (ICAM-1) on the cell surface is sufficient to trigger MTOC polarization in the HTLV-1-infected T cell. However, the mechanism by which Tax and ICAM-1 cause the MTOC polarization is not fully understood. Here we show that the presence of Tax at the MTOC region and its ability to stimulate cyclic AMP-binding protein-dependent pathways are both required for MTOC polarization in the HTLV-1-infected T cell at the virological synapse. Furthermore, we show that the MTOC polarization induced by ICAM-1 engagement depends on activation of the Ras-MEK-ERK signaling pathway. Our findings indicate that efficient MTOC polarization at the virological synapse requires Tax-mediated stimulation of T-cell activation pathways in synergy with ICAM-1 cross-linking. The results also reveal differences in the signaling pathways used to trigger MTOC polarization between the immunologic synapse and the virological synapse.

The prevalence of syphilis in HIV-seropositive patients: a retrospective study at the regional hospital in Agadir, Morocco.

INTRODUCTION: HIV and syphilis are major public health problems in Morocco. The region of Souss-Massa, south-west of the country, hold more than 24% of HIV seropositive cases registered in Morocco during 2009. The aim of this study is to evaluate the seroprevalence of syphilis among HIV seropositive patients in the region of Souss-Massa, south-west of Morocco. METHODS: To evaluate the seroprevalence of syphilis and neurosyphilis among HIV seropositive patients, we retrospectively investigated the medical records of HIV-infected patients attending the regional hospital located in the city of Agadir, during the period comprised between 2011 and 2016. RESULTS: The population studied involved 1381 males (49.18%) and 1427 females (50.82%) HIV seropositive patients. Among them, 481 patients were seropositive for syphilis and three cases were diagnosed with neurosyphilis. The sex ratio distribution was 243 male (52.71%) and 218 female (47.29%). The prevalence of syphilis among the studied population was estimated to 16.42% with a slight dominance in male (17.63%) compared to female (15.28%). By contrast, neurosyphilis was only detected in male patients, with a prevalence estimated to 0.11%. CONCLUSION: Even if the prevalence of HIV and syphilis is stable in the region of Souss-Massa, the prevalence of syphilis among HIV seropositive patients remained high and correlated positively with that of HIV infection. We did not find a significant difference between the genders, in relation to the prevalence of HIV and syphilis. We concluded that it was essential to continue monitoring the population, in order to improve the prevention and the access to the medical care in the south-west of Morocco.

Interferons alpha and gamma induce p53-dependent and p53-independent apoptosis, respectively.

Type I interferon (IFN) enhances the transcription of the tumor suppressor gene p53. To elucidate the molecular mechanism mediating IFN-induced apoptosis, we analysed programmed cell death in response to type I (IFNalpha) or type II (IFNgamma) treatment in relation to p53 status. In two cell lines (MCF-7, SKNSH), IFNalpha, but not IFNgamma, enhanced apoptosis in a p53-dependent manner. Furthermore, only IFNalpha upregulated p53 as well as p53 target genes (Noxa, Mdm2 and CD95). The apoptotic response to IFNalpha decreased in the presence of ZB4, an anti-CD95 antibody, suggesting that CD95 is involved in this process. When p53 was inactivated by the E6 viral protein or the expression of a p53 mutant, IFNalpha-induced apoptosis and p53 target genes upregulation were abrogated. Altogether these results demonstrate that p53 plays a pivotal role in the IFNalpha-induced apoptotic response. IFNalpha-induced PML was unable to recruit p53 into nuclear bodies and its downregulation by siRNA did not alter CD95 expression. In contrast, IFNgamma-induced apoptosis is p53-independent. CD95 and IFN-regulatory factor 1 (IRF1) are directly upregulated by this cytokine. Apoptotic response to IFNgamma is decreased in the presence of ZB4 and strongly diminished by IRF1 siRNA, implicating both CD95 and IRF1 in IFNgamma-induced apoptotic response. Taken together, these results show that in two different cell lines, IFNalpha and IFNgamma, induce p53-dependent -independent apoptosis, respectively.

The HTLV-1 Virological Synapse.

Human T-lymphotropic virus-1 (HTLV-1) spreads efficiently between T-cells via a tight and highly organized cell-cell contact known as the virological synapse. It is now thought that many retroviruses and other viruses spread via a virological synapse, which may be defined as a virus-induced, specialized area of cell-to-cell contact that promotes the directed transmission of the virus between cells. We summarize here the mechanisms leading to the formation of the HTLV-1 virological synapse and the role played by HTLV-1 Tax protein. We propose a model of HTLV-1 transmission between T-cells based on the three-dimensional ultrastructure of the virological synapse. Finally, in the light of recent advances, we discuss the possible routes of HTLV-1 spread across the virological synapse.

The immune control of HTLV-1 infection: selection forces and dynamics.

Cytotoxic T lymphocytes (CTLs) play a central role in the protective immune response to human T-lymphotropic virus 1 (HTLV-1). Here we consider two questions. First, what determines the strength of an individual's HTLV-1-specific CTL response? Second, what controls the rate of expression of HTLV-1 in vivo, which is greater in patients with HAM/TSP than in asymptomatic carriers with the same proviral load? Recent evidence shows that FoxP3+CD4+ T cells are abnormally frequent in HTLV-1 infection, and the frequency of these cells is inversely correlated with the rate of CTL lysis of HTLV-1-infected cells, suggesting that FoxP3+CD4+ cell frequency is an important determinant of the outcome of HTLV-1 infection. There is also new evidence that the rate of expression of HTLV-1 in vivo is associated with the transcriptional activity of the flanking host genome. We suggest that the frequencies of HTLV-1-infected T cell clones in vivo are determined by a dynamic balance between positive and negative selection forces that differ among the clones.

Human T-lymphotropic virus-1 visualized at the virological synapse by electron tomography.

Human T-lymphotropic virus 1 (HTLV-1) is transmitted directly between cells via an organized cell-cell contact called a virological synapse (VS). The VS has been studied by light microscopy, but the ultrastructure of the VS and the nature of the transmitted viral particle have remained unknown. Cell-free enveloped virions of HTLV-1 are undetectable in the serum of individuals infected with the human T-lymphotropic virus 1 (HTLV-1) and during in vitro culture of naturally infected lymphocytes. However, the viral envelope protein is required for infectivity of HTLV-1, suggesting that complete, enveloped HTLV-1 virions are transferred across the synapse. Here, we use electron tomography combined with immunostaining of viral protein to demonstrate the presence of enveloped HTLV-1 particles within the VS formed between naturally infected lymphocytes. We show in 3D that HTLV-1 particles can be detected in multiple synaptic clefts at different locations simultaneously within the same VS. The synaptic clefts are surrounded by the tightly apposed plasma membranes of the two cells. HTLV-1 virions can contact the recipient cell membrane before detaching from the infected cell. The results show that the HTLV-1 virological synapse that forms spontaneously between lymphocytes of HTLV-1 infected individuals allows direct cell-cell transmission of the virus by triggered, directional release of enveloped HTLV-1 particles into confined intercellular spaces.

Human T-lymphotropic virus, type 1, tax protein triggers microtubule reorientation in the virological synapse.

We showed recently that the human T-lymphotropic virus, type 1 (HTLV-1), spreads directly from cell to cell via a virological synapse. The HTLV-1 virological synapse resembles the immunological synapse; each is a specialized contact between a lymphocyte and another cell that contains organized protein microdomains, and each involves repolarization of the T-cell microtubule cytoskeleton. However, formation of the virological synapse is not triggered by T-cell receptor-mediated antigen recognition. On the basis of our previous data, we postulated that formation of the viral synapse was triggered by a conjunction of two signals, one from HTLV-1 infection of the T-cell and one from cell-cell contact. We have recently identified ICAM-1 engagement as a cell-contact signal that causes the microtubule polarization associated with the virological synapse. Here we used confocal microscopy of T-lymphocytes naturally infected with HTLV-1 or transfected with individual HTLV-1 genes to investigate the role of the viral transcriptional transactivator protein Tax. Polarization of the microtubules was induced by cell-cell contact or by cross-linking T-cell surface molecules with monoclonal antibodies adsorbed to latex beads. We show that Tax, which is mainly found in the nucleus, is also present at two specific extranuclear sites as follows: around the microtubule organizing center in association with the cis-Golgi and in the cell-cell contact region. We show that expression of Tax provides an intracellular signal that synergizes with ICAM-1 engagement to cause the T-cell microtubule polarization observed at the virological synapse.

Different MHC class I heavy chains compete with each other for folding independently of beta 2-microglobulin and peptide.

We reported previously that different MHC class I molecules can compete with each other for cell surface expression in F(1) hybrid and MHC class I transgenic mice. In this study, we show that the competition also occurs in transfected cell lines, and investigate the mechanism. Cell surface expression of an endogenous class I molecule in Chinese hamster ovary (CHO) cells was strongly down-regulated when the mouse K(d) class I H chain was introduced by transfection. The competition occurred only after K(d) protein translation, not at the level of RNA, and localization studies of a CHO class I-GFP fusion showed that the presence of K(d) caused retention of the hamster class I molecule in the endoplasmic reticulum. The competition was not for beta(2)-microglobulin, because a single chain version of K(d) that included mouse beta(2)-microglobulin also had a similar effect. The competition was not for association with TAP and loading with peptide, because a mutant form of the K(d) class I H chain, not able to associate with TAP, caused the same down-regulation of hamster class I expression. Moreover, K(d) expression led to a similar level of competition in TAP2-negative CHO cells. Competition for cell surface expression was also found between different mouse class I H chains in transfected mouse cells, and this competition prevented association of the H chain with beta(2)-microglobulin. These unexpected new findings show that different class I H chains compete with each other at an early stage of the intracellular assembly pathway, independently of beta(2)-microglobulin and peptide.