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Viral fitness, the replicative adaptation of a virus to its environment, has viral and environmental determinants. Presently, growth competition assays of recombinant viruses can supply a precise evaluation of this parameter of potential clinical interest. On the basis of the data obtained by monitoring viral infections under treatment with antiviral compounds and by sequence-function analysis of drug-resistant variants, it has recently been proposed that intentional selection of viral mutants with reduced fitness could be an efficient antiviral strategy in several important viral infections of humans. From this point of view, specific antiviral compounds as well as human monoclonal antibodies targeting crucial viral proteins could be effective in modifying the viral replication capacity and the pathogenic potential of rapidly evolving RNA viruses that are normally able to escape under the pressure of treatments with single or multiple antiviral drugs. [Copyright &y& Elsevier]

The aim of our study was to describe the incidence and predictive factors of secondary infections in patients with coronavirus disease 2019 (COVID-19). This was a cohort study of patients hospitalized with COVID-19 at IRCCS San Raffaele Hospital between 25th February and 6th April 2020 (NCT04318366). We considered secondary bloodstream infections (BSIs) or possible lower respiratory tract infections (pLRTIs) occurring 48 hours after hospital admission until death or discharge. We calculated multivariable Fine–Gray models to assess factors associated with risk of secondary infections. Among 731 patients, a secondary infection was diagnosed in 68 patients (9.3%); 58/731 patients (7.9%) had at least one BSI and 22/731 patients (3.0%) at least one pLRTI. The overall 28-day cumulative incidence was 16.4% (95%CI 12.4–21.0%). Most of the BSIs were due to Gram-positive pathogens (76/106 isolates, 71.7%), specifically coagulase-negative staphylococci (53/76, 69.7%), while among Gram-negatives (23/106, 21.7%) Acinetobacter baumanii (7/23, 30.4%) and Escherichia coli (5/23, 21.7%) predominated. pLRTIs were caused mainly by Gram-negative pathogens (14/26, 53.8%). Eleven patients were diagnosed with putative invasive aspergillosis. At multivariable analysis, factors associated with secondary infections were low baseline lymphocyte count (≤0.7 versus >0.7 per 109/L, subdistribution hazard ratios (sdHRs) 1.93, 95%CI 1.11–3.35), baseline PaO 2 /FiO 2 (per 100 points lower: sdHRs 1.56, 95%CI 1.21–2.04), and intensive-care unit (ICU) admission in the first 48 hours (sdHR 2.51, 95%CI 1.04–6.05). Patients hospitalized with COVID-19 had a high incidence of secondary infections. At multivariable analysis, early need for ICU, respiratory failure, and severe lymphopenia were identified as risk factors for secondary infections. [ABSTRACT FROM AUTHOR]

Objective: To study the impact of asymptomatic semen infections on seminal parameters in men presenting for primary couple's infertility.Design: Cross-sectional study.Setting: Academic center.Patients: Socio-demographic, clinical, and laboratory data from 1689 infertile men were analyzed.Intervention(s): Semen analysis was based on 2010 World Health Organization reference criteria. Each patient underwent semen culture test to identify common urogenital pathogens. Infections by Mycoplasma, Ureaplasma, and Chlamydia spp. were evaluated through a real time polymerase chain reaction platform. Descriptive statistics and linear and logistic regression models were used to test the association between semen infections and clinical, seminal, and hormonal parameters.Main Outcome Measure(s): Prevalence of asymptomatic semen infection and impact of semen infection on sperm parameters.Results: Of 1689 men, 354 (21.0%) had an asymptomatic positive semen culture. Ureaplasma urealyticum (37.6%) was the most frequent single pathogen, followed by Enterobacteriaceae (any type; 24.8%), other pathogens (20.3%), Chlamydia trachomatis (3.4%) and Mycoplasma spp (3.4%). Positive semen cultures were associated with lower sperm concentrations (P<0.001) and progressive motility (P<.001). These latter findings were mostly particular to men with infections caused by Ureaplasma urealyticum compared with negative semen cultures. A positive semen culture was both univariably (P<.001) and multivariably (P=.04) associated with a lower sperm concentration.Conclusion: One out of five men presenting for a couple's primary infertility had asymptomatic semen infections, which were significantly associated with impaired sperm concentration. These observations point out the importance of an accurate investigation of semen infection in the everyday clinical practice diagnostic workup of infertile men. [ABSTRACT FROM AUTHOR]

The global burden of herpes simplex virus (HSV) legitimates the critical need to develop new prevention strategies, such as drugs and vaccines that are able to fight either primary HSV infections or reactivations. Moreover, the ever-growing number of patients receiving transplants increases the number of severe HSV infections that are unresponsive to current therapies. Finally, the high global incidence of genital HSV-2 infection increases the risk of perinatal transmission to newborns, in which disseminated infection or central nervous system (CNS) involvement is frequent, with associated high morbidity and mortality rates. There are several key features shared by novel anti-HSV drugs, from currently available optimized drugs to small molecules able to interfere with various virus replication steps. However, several virological aspects of the disease and associated clinical needs highlight why an ideal anti-HSV drug has yet to be developed. [ABSTRACT FROM AUTHOR]

The lack of structural information on hepatitis C virus (HCV) surface proteins has so far hampered the development of effective vaccines. Recently, two crystallographic structures have described the core portion (E2c) of E2 surface glycoprotein, the primary mediator of HCV entry. Despite the importance of these studies, the E2 overall structure is still unknown and, most importantly, several biochemical and functional studies are in disagreement with E2c structures. Here, the main literature will be discussed and an alternative disulfide bridge pattern will be proposed, based on unpublished human monoclonal antibody reactivity. A modeling strategy aiming at recapitulating the available structural and functional studies of E2 will also be proposed. [ABSTRACT FROM AUTHOR]

Monoclonal antibodies (mAbs) have been used successfully both in research and for clinical purposes. The possible use of protective mAbs directed against different microbial pathogens is currently being considered. The fine definition of the epitope recognized by a protective mAb is an important aspect to be considered for possible development in epitope-based vaccinology. The most accurate approach to this is the X-ray resolution of mAb/antigen crystal complex. Unfortunately, this approach is not always feasible. Under this perspective, several surrogate epitope mapping strategies based on the use of bioinformatics have been developed. In this article, we review the most common, freely accessible, bioinformatic tools used for epitope characterization and provide some basic examples of molecular visualization, editing and computational analysis. [Copyright &y& Elsevier]

Abstract: A study aiming at cloning and characterizing natural antibodies to human immunodeficiency virus type 1 (HIV-1) targets is described. In particular, we report the molecular cloning of a Fab molecule binding the HIV-1/Tat protein from a seronegative patient. The Fab was characterized for its binding specificity and investigated in regards to its molecular structure. Furthermore, to evaluate the role played by the heavy and light chains in the binding to the antigen, hybrid Fabs were constructed combining the heavy and the light chain of the natural anti-Tat clone with a control high-affinity Fab derived from the repertoire of the same patient. The results indicate that the natural immunoglobulin under study: (i) is a polyreactive antibody of IgG1 isotype, and not an IgM as usually described for anti-HIV natural clones, (ii) shows a pattern of mutations compatible with an antigen-driven mechanisms, (iii) its heavy chain derives from a V-gene subfamily (V3-23) highly represented in fetal life, and (iv) its heavy chain variable region exhibits several characteristics, including an extremely long, hydrophilic CDR3, that are unusual and theoretically important in determining the polyreactive capacity of the molecule. [Copyright &y& Elsevier]