Genetic and phylogenetic evolution of HIV-1 in a low subtype heterogeneity epidemic: the Italian example

The Human Immunodeficiency Virus type 1 (HIV-1) is classified into genetic groups, subtypes and sub-subtypes which show a specific geographic distribution pattern. The HIV-1 epidemic in Italy, as in most of the Western Countries, has traditionally affected the Intra-venous drug user (IDU) and Homosexual (Homo) risk groups and has been sustained by the genetic B subtype. In the last years, however, the HIV-1 transmission rate among heterosexuals has dramatically increased, becoming the prevalent transmission route. In fact, while the traditional risk groups have high levels of knowledge and avoid high-risk practices, the heterosexuals do not sufficiently perceive the risk of HIV-1 infection. This misperception, linked to the growing number of immigrants from non-Western Countries, where non-B clades and circulating recombinant forms (CRFs) are prevalent, is progressively introducing HIV-1 variants of non-B subtype in the Italian epidemic. This is in agreement with reports from other Western European Countries

Conformational HIV-1 Envelope on particulate structures: a tool for chemokine coreceptor binding studies

The human immunodeficiency virus type 1 (HIV-1) external envelope glycoprotein gp120 presents conserved binding sites for binding to the primary virus receptor CD4 as well as the major HIV chemokine coreceptors, CCR5 and CXCR4

Effects of adjuvants on IgG subclasses elicited by virus-like Particles

<p>Abstract</p> <p>Background</p> <p>Virus-Like Particles (VLPs) represent an efficient strategy to present and deliver conformational antigens to the immune system, inducing both arms of the adaptive immune response. Moreover, their particulate structure surrounded by cell membrane provides an adjuvanted effect to VLP-based immunizations. In the present study, the elicitation of different patterns of IgG subclasses by VLPs, administered in CpG ODN1826 or poly(I:C) adjuvants, has been evaluated in an animal model.</p> <p>Results</p> <p>Adjuvanted VLPs elicited a higher titer of total specific IgG compared to VLPs alone. Furthermore, while VLPs alone induced a balanced T_H2 pattern, VLPs formulated with either adjuvant elicited a T_H1-biased IgG subclasses (IgG2a and IgG3), with poly(I:C) more potent than CpG ODN1826.</p> <p>Conclusions</p> <p>The results confirmed that adjuvants efficiently improve antigen immunogenicity and represent a suitable strategy to skew the adaptive immune response toward the differentiation of the desired T helper subset, also using VLPs as antigen.</p

Challenges in cancer vaccine development for hepatocellular carcinoma

SummaryHepatocellular carcinoma (HCC) is the most common liver malignancy, representing the third and fifth leading cause of death from cancer worldwide in men and women, respectively.The main risk factor for the development of HCC is the hepatitis B and C virus (HBV and HCV) infection; non-viral causes (e.g., alcoholism and aflatoxin) are additional risk factors.HCC prognosis is generally poor because of the low effectiveness of available treatments and the overall 5-year survival rate is approximately 5–6%.In this framework, immunotherapeutic interventions, including cancer vaccines, may represent a novel and effective therapeutic tool. However, only few immunotherapy trials for HCC have been conducted so far with contrasting results, suggesting that improvements in several aspects of the immunotherapy approaches need to be implemented.In particular, identification of novel specific tumor antigens and evaluation of most advanced combinatorial strategies could result in unprecedented clinical outcomes with great beneficial effect for HCC patients.The state of the art in immunotherapy strategies for HCC and future perspectives are reported in the present review

The Molecular Interplay between Human Oncoviruses and Telomerase in Cancer Development

Funding Information: This work was supported by the Italian Ministry of Health Ricerca Corrente 2022 Grant L1/10. M.I. Isaguliants was supported by the Latvian Science Fund, project LZP 2021/1-0484. Publisher Copyright: © 2022 by the authors.Human oncoviruses are able to subvert telomerase function in cancer cells through multiple strategies. The activity of the catalytic subunit of telomerase (TERT) is universally enhanced in virus-related cancers. Viral oncoproteins, such as high-risk human papillomavirus (HPV) E6, Epstein–Barr virus (EBV) LMP1, Kaposi’s sarcoma-associated herpesvirus (HHV-8) LANA, hepatitis B virus (HBV) HBVx, hepatitis C virus (HCV) core protein and human T-cell leukemia virus-1 (HTLV-1) Tax protein, interact with regulatory elements in the infected cells and contribute to the transcriptional activation of TERT gene. Specifically, viral oncoproteins have been shown to bind TERT promoter, to induce post-transcriptional alterations of TERT mRNA and to cause epigenetic modifications, which have important effects on the regulation of telomeric and extra-telomeric functions of the telomerase. Other viruses, such as herpesviruses, operate by integrating their genomes within the telomeres or by inducing alternative lengthening of telomeres (ALT) in non-ALT cells. In this review, we recapitulate on recent findings on virus–telomerase/telomeres interplay and the importance of TERT-related oncogenic pathways activated by cancer-causing viruses.publishersversionPeer reviewe

Systems biology applied to vaccine and immunotherapy development

Immunotherapies, including vaccines, represent a potent tool to prevent or contain disease with high morbidity or mortality such as infections and cancer. However, despite their widespread use, we still have a limited understanding of the mechanisms underlying the induction of protective immune responses

Prevalence of human papillomavirus genotypes and their variants in high risk West Africa women immigrants in South Italy

BACKGROUND: The distribution of human papillomaviruses (HPVs) varies greatly across populations and HPV surveys have been performed in different geographical regions in order to apply appropriate vaccine strategies. Little information, however, exists regarding HPV genotypes distribution in immigrant women from countries at high incidence for cervical cancer. The aim of this study was to determine the spectrum of HPVs and their variants among HIV-positive and HIV-negative women immigrants in South Italy mainly from West Africa and with a history of prostitution. RESULTS: Cervical cytological samples have been collected from 14 HIV-positive and 31 HIV-negative immigrants (38 out of 45 were born in Nigeria), attending a gynecological outpatient clinic in the Campania region. Human papillomaviruses were detected by broad spectrum consensus-primer-pairs MY09/MY11 and GP5+/GP6+-based polymerase chain reaction and characterized by nucleotide sequence analysis. Altogether, 42.2% (19/45) of samples were HPV positive with detection rates of 57.1% (8/14) in HIV-positive and 35.5% (11/31) in HIV-negative women. Among the twelve different viral genotypes identified, HPV33, 58, 70 and 81 were the prevalent genotypes with a frequency of 6.7% each, followed by HPV16, 35, 42, 54, 31, 52, 56 and 67, in descending order of prevalence. Sequence homology studies performed on the L1 amplified fragments of HPV16, 52 and 58 isolates allowed the identification of nucleotide changes distinctive of non-European variants. CONCLUSION: The overall HPV prevalence (42.2%) was high in this immigrant women group with the most common viral types other than HPV16 and 18, against which current vaccine strategies have been developed. The distribution of HPV genotypes and their variants in high-risk immigrants reflects that of their original countries. The surveillance of risk groups that may act as viral reservoirs of uncommon genotypes within different countries are necessary to determine the severity of HPV infection with the different viral types and to monitor a possible shift of prevalent strains following vaccination

Functional Interaction between Human Papillomavirus Type 16 E6 and E7 Oncoproteins and Cigarette Smoke Components in Lung Epithelial Cells

The smoking habit is the most important, but not a sufficient cause for lung cancer development. Several studies have reported the human papillomavirus type 16 (HPV16) presence and E6 and E7 transcripts expression in lung carcinoma cases from different geographical regions. The possible interaction between HPV infection and smoke carcinogens, however, remains unclear. In this study we address a potential cooperation between tobacco smoke and HPV16 E6 and E7 oncoproteins for alterations in proliferative and tumorigenic properties of lung epithelial cells. A549 (alveolar, tumoral) and BEAS-2B (bronchial, non-tumoral) cell lines were stably transfected with recombinant pLXSN vectors expressing HPV16 E6 and E7 oncoproteins and exposed to cigarette smoke condensate (CSC) at different concentrations. HPV16 E6 and E7 expression was associated with loss of p53 stability, telomerase (hTERT) and p16INK4A overexpression in BEAS-2B cells as demonstrated by quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting (WB). In A549 cells we observed downregulation of p53 but not a significant increase of hTERT transcripts. In addition, the HPV16 E6/E7 transfected cell lines showed an increased proliferation rate and anchorage-independent growth in a HPV16 E6 and E7 expression-dependent manner. Moreover, both HPV16 E6/E7 and mock transfected cells showed an increased proliferation rate and anchorage-independent growth in the presence of 0.1 and 10 µg/mL CSC. However, this increase was significantly greater in HPV16 E6/E7 transfected cells (p<0.001). Data were confirmed by FCSE proliferation assay. The results obtained in this study are suggestive of a functional interaction between tobacco smoke and HPV16 E6/E7 oncoproteins for malignant transformation and tumorigenesis of lung epithelial cells. More studies are warranted in order to dissect the molecular mechanisms involved in this cooperation

Immature monocyte derived dendritic cells gene expression profile in response to Virus-Like Particles stimulation

We have recently developed a candidate HIV-1 vaccine model based on HIV-1 Pr55gag Virus-Like Particles (HIV-VLPs), produced in a baculovirus expression system and presenting a gp120 molecule from an Ugandan HIV-1 isolate of the clade A (HIV-VLP(A)s). The HIV-VLP(A)s induce in Balb/c mice systemic and mucosal neutralizing Antibodies as well as cytotoxic T lymphocytes, by intra-peritoneal as well as intra-nasal administration. Moreover, we have recently shown that the baculovirus-expressed HIV-VLPs induce maturation and activation of monocyte-derived dendritic cells (MDDCs) which, in turn, produce Th1- and Th2-specific cytokines and stimulate in vitro a primary and secondary response in autologous CD4+ T cells. In the present manuscript, the effects of the baculovirus-expressed HIV-VLP(A)s on the genomic transcriptional profile of MDDCs obtained from normal healthy donors have been evaluated. The HIV-VLP(A )stimulation, compared to both PBS and LPS treatment, modulate the expression of genes involved in the morphological and functional changes characterizing the MDDCs activation and maturation. The results of gene profiling analysis here presented are highly informative on the global pattern of gene expression alteration underlying the activation of MDDCs by HIV-VLP(A)s at the early stages of the immune response and may be extremely helpful for the identification of exclusive activation markers