Significance: Non-Hodgkin lymphomas (NHLs) are associated with HIV-1 infection, but the HIV1 genome is not detectable in malignant B cells. Here we show that variants of the HIV-1 matrix protein p17 (vp17s) are detected in the NHL specimens of HIV+ patients. These vp17s are more frequently detected in HIV+ patients with NHL than in patients without NHL. These vp17s display a potent B-cell growth-promoting activity, which is exerted by activating the Akt signaling pathway. Results obtained by CD spectroscopy and thermal denaturation suggest that mutation-induced protein destabilization may lead to a conformational change potentially responsible for the viral protein to promote B-cell growth. Our results suggest that vp17s may have a role in sustaining lymphomagenesis, thus offering new opportunities to prevent and/or treat HIV-associated NHLs.

Background: The first influenza pandemic of the 21th century was ignited by a new strain of influenza A virus (A/H1N1pdm). Specific patient groups, including those with comorbidities, pregnant women, young children, older and immunocompromised patients, are at increased risk for serious influenza-related disease. This study was aimed at investigating the influence of clinical presentation, antiviral treatment and possible drug resistance-associated mutations, on the extent and duration of viral shedding in patients infected with A/H1N1pdm. Methods: An observational study was performed, based on retrospective review of clinical and laboratory records of patients who were hospitalized for A/H1N1pdm infection at the National Institute for Infectious Diseases "L. Spallanzani", Rome, Italy, between April 24 and December 31, 2009. Among 119 hospitalized patients, 39 were selected for a post hoc analysis, based on the availability of serial nasopharyngeal swabs samples and related information. Results: Eleven out of the 39 study patients (28.2%) presented with pneumonia; 29 (74.4%) received antiviral treatment. Patients with pneumonia were significantly older than patients without pneumonia. The mean values of viral RNA concentration were not significantly increased in patients with pneumonia, but a significant increase in the duration of viral shedding was observed as compared to patients without pneumonia. In patients receiving antivirals, the viral RNA concentration was significantly reduced in comparison to untreated patients at days 4-5 after symptom onset, while the overall duration of viral shedding was only marginally affected. A significant correlation between duration of viral shedding and time elapsed between symptom onset and therapy start was observed, with a significant reduction of days of viral shedding when therapy was initiated within 2 days of symptoms appearance. No known drug resistance mutations were detected in patients with prolonged viral shedding. Conclusions: Our results show that severe respiratory illness is associated with delayed virus clearance in patients with A/H1N1pdm infection. Antivirals caused an early reduction of viral load, but only marginally affected the overall duration of shedding. Prolonged shedding was not associated with the emergence of strains carrying known drug-resistance mutations.

To evaluate if the administration of highly active antiretroviral therapy (HAART) during primary HIV infection (PHI) may affect the antibody avidity evolution. In 13 subjects with symptomatic PHI, of whom 8 initiated HAART at diagnosis, the Avidity Index (AI) and Western blot evolution patterns were analyzed on serial serum/plasma samples for 1 year. In 4 patients, who subsequently interrupted HAART, additional specimens were analyzed. At diagnosis, the range of HIV viremia was 0.003 to 38 × 106 copies/mL. In untreated patients, viremia reached the set point in 4 to 6 months, whereas in treated patients, early suppression of viremia was observed, remaining undetectable during therapy. At diagnosis, the median AI was low in untreated (0.42, range: 0.33 to 0.43) and treated (0.44, range: 0.40 to 0.72) patients. At 3, 6, and 12 months, the AI progressively increased in untreated patients, whereas it remained <0.80 in all treated patients. In the 4 patients interrupting HAART, the AI increased after therapy interruption to greater than 0.80 in ≤6 months. The Western blot pattern transiently/partially reversed during HAART in 2 patients. Antibody avidity maturation takes place only in the presence of ongoing viral replication. These results may have relevant implications in understanding the complex mechanism of maturation of the immune response to HIV.

In January 2015, during a 3-week period, 12 captive Tonkean macacques at a sanctuary in Italy died. An orthopoxvirus infection was suspected because of negative-staining electron microscopy results. The diagnosis was confirmed by histology, virus isolation, and molecular analysis performed on different organs from all animals. An epidemiologic investigation was unable to define the infection source in the surrounding area. Trapped rodents were negative by virologic testing, but specific IgG was detected in 27.27% of small rodents and 14.28% of rats. An attenuated live vaccine was administered to the susceptible monkey population, and no adverse reactions were observed; a detectable humoral immune response was induced in most of the vaccinated animals. We performed molecular characterization of the orthopoxvirus isolate by next-generation sequencing. According to the phylogenetic analysis of the 9 conserved genes, the virus could be part of a novel clade, lying between cowpox and ectromelia viruses.

This study was aimed at establishing the genetic heterogeneity of influenza virus haemagglutinin (HA) gene quasi-species and the polymorphisms at codon 222, by application of ultra-deep pyrosequencing (UDPS) to respiratory samples from patients hospitalized for influenza A(H1N1)pdm09 infection, presenting with severe or moderate–mild disease. HA diversity was significantly higher in samples collected from patients with severe manifestations than in those from patients with moderate–mild manifestations (p 0.02). D222 polymorphism was detected in 40.7% of patients by UDPS, and in only 7.1% by Sanger sequencing. D222E, D222G, D222N and D222A were observed in 37.0%, 11.1%, 7.4% and 3.7% of patients, respectively; 10.7% of samples harboured more than two variants. The relative frequency of each single variant showed a wide range of intrapatient variation. D222G/N/A were detected, as either minor or predominant variants, only in severe cases, whereas D222E was equally represented in severe and moderate–mild infections. Other amino acid variants were observed at different positions within the analysed HA fragment. Consistent with higher heterogeneity, non-D222 variants were more frequently detected in severe cases than in moderate–mild cases. In addition, seven non-D222 mutations carried by minority variants, not previously described, were observed.