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Circulating recombinant forms (CRFs) are important components of the HIV-1 pandemic. Among 110 reported in the literature, 17 are BF1 intersubtype recombinant, most of which are of South American origin. Among these, all 5 identified in the Southern Cone and neighboring countries, except Brazil, derive from a common recombinant ancestor related to CRF12_BF, which circulates widely in Argentina, as deduced from coincident breakpoints and clustering in phylogenetic trees. In a HIV-1 molecular epidemiological study in Spain, we identified a phylogenetic cluster of 20 samples from 3 separate regions which were of F1 subsubtype, related to the Brazilian strain, in protease-reverse transcriptase (Pr-RT) and of subtype B in integrase. Remarkably, 14 individuals from this cluster (designated BF9) were Paraguayans and only 4 were native Spaniards. HIV-1 transmission was predominantly heterosexual, except for a subcluster of 6 individuals, 5 of which were men who have sex with men. Ten additional database sequences, from Argentina (n = 4), Spain (n = 3), Paraguay (n = 1), Brazil (n = 1), and Italy (n = 1), branched within the BF9 cluster. To determine whether it represents a new CRF, near full-length genome (NFLG) sequences were obtained for 6 viruses from 3 Spanish regions. Bootscan analyses showed a coincident BF1 recombinant structure, with 5 breakpoints, located in p17 gag , integrase, gp120, gp41-rev overlap, and nef, which was identical to that of two BF1 recombinant viruses from Paraguay previously sequenced in NFLGs. Interestingly, none of the breakpoints coincided with those of CRF12_BF. In a maximum likelihood phylogenetic tree, all 8 NFLG sequences grouped in a strongly supported clade segregating from previously identified CRFs and from the CRF12_BF "family" clade. These results allow us to identify a new HIV-1 CRF, designated CRF66_BF. Through a Bayesian coalescent analysis, the most recent common ancestor of CRF66_BF was estimated around 1984 in South America, either in Paraguay or Argentina. Among Pr-RT sequences obtained by us from HIV-1-infected Paraguayans living in Spain, 14 (20.9%) of 67 were of CRF66_BF, suggesting that CRF66_BF may be one of the major HIV-1 genetic forms circulating in Paraguay. CRF66_BF is the first reported non-Brazilian South American HIV-1 CRF_BF unrelated to CRF12_BF. This work was funded through Acción Estratégica en Salud Intramural (AESI), Instituto de Salud Carlos III, projects PI16CIII/00033 and PI19CIII/00042; Red de Investigación en SIDA (RIS), Instituto de Salud Carlos III, Subdirección General de Evaluación y Fondo Europeo de Desarrollo Regional (FEDER), Plan Nacional I+D+I, project RD16ISCIII/0002/0004; and scientific agreements with Consellería de Sanidade, Government of Galicia (MVI 1004/16) and Osakidetza-Servicio Vasco de Salud, Government of Basque Country (MVI 1001/16). Sí

[Abstract] A percentage of hepatitis C virus (HCV)-infected patients fail direct acting antiviral (DAA)-based treatment regimens, often because of drug resistance-associated substitutions (RAS). The aim of this study was to characterize the resistance profile of a large cohort of patients failing DAA-based treatments, and investigate the relationship between HCV subtype and failure, as an aid to optimizing management of these patients. A new, standardized HCV-RAS testing protocol based on deep sequencing was designed and applied to 220 previously subtyped samples from patients failing DAA treatment, collected in 39 Spanish hospitals. The majority had received DAA-based interferon (IFN) α-free regimens; 79% had failed sofosbuvir-containing therapy. Genomic regions encoding the nonstructural protein (NS) 3, NS5A, and NS5B (DAA target regions) were analyzed using subtype-specific primers. Viral subtype distribution was as follows: genotype (G) 1, 62.7%; G3a, 21.4%; G4d, 12.3%; G2, 1.8%; and mixed infections 1.8%. Overall, 88.6% of patients carried at least 1 RAS, and 19% carried RAS at frequencies below 20% in the mutant spectrum. There were no differences in RAS selection between treatments with and without ribavirin. Regardless of the treatment received, each HCV subtype showed specific types of RAS. Of note, no RAS were detected in the target proteins of 18.6% of patients failing treatment, and 30.4% of patients had RAS in proteins that were not targets of the inhibitors they received. HCV patients failing DAA therapy showed a high diversity of RAS. Ribavirin use did not influence the type or number of RAS at failure. The subtype-specific pattern of RAS emergence underscores the importance of accurate HCV subtyping. The frequency of “extra-target” RAS suggests the need for RAS screening in all three DAA target regions. Ministerio de Economía y Empresa; IDI-20151125 Ministerio de Ciencia, Innovación y Universidades; SAF SAF 2017-87846-R

Since hepatitis C virus (HCV) and human T-lymphotropic virus (HTLV) share transmission routes, dual infection could be frequent. In Spain, HTLV underdiagnosis is highlighted by the high proportion of patients presenting either with tropical spastic paraparesis or adult T cell leukemia at first diagnosis. We examined whether the renewed efforts for expanding HCV testing may provide a sentinel population that might selectively be targeted to unveil asymptomatic HTLV carriers. The presence of anti-HTLV antibodies was examined in 3,838 consecutive individuals with reactive HCV serology attended during the last 3 years at 13 hospitals distributed across the Spanish geography. Overall 71% were male, and the median age was 41 years old. Foreigners represented 9% of the study population. A total of 50 individuals (1.3%) were seroreactive for HTLV, being 30 confirmed as HTLV-2 and 2 as HTLV-1 (0.12%). The remaining 18 had indeterminate Western blot patterns. Most individuals with HTLV-2 and HTLV indetermi...

Spanish HTLV Network., [Background] Human retroviruses HIV and HTLV share transmission routes. HIV widely spread in Spain during the 80 s through injection drug use and sex, and nowadays HIV rates in Spain account for one of the largest in Europe. In contrast, HTLV-1 is not endemic in Spain, despite hosting huge numbers of migrants from highly endemic regions. Herein, we report the rate and main features of the HIV-HTLV co-infected population in Spain., [Methods] A national registry exists in Spain for HTLV since year 1989. Data from standardized case report forms and one centralized lab repository were reviewed, especially for the subset with HTLV-HIV co-infection. [Results] Up to December 2018, a total of 369 individuals with HTLV-1 had been diagnosed in Spain. 64% of the population were females, and Latin American individuals accounted for 64.5%. Classical HTLV-associated illnesses were found in 12.7% (myelopathy) and 7.6% (leukemia). HIV coinfection was found in 12 (3.2%). Of those, 3 patients (25%) were female and 39 (75%) were of non-Spanish origin. All but two harbored HIV-1 subtype B, being non-B variants found in the two West Africans. Exposure had been sexual in most cases, being 4 homosexual men. Seven HTLV-HIV co-infected patients had developed AIDS and two had developed myelopathy. There was no evidence for increased HTLV-1 clinical pathogenicity due to HIV coinfection. [Conclusion] HIV coinfection is infrequent (

Human T-lymphotropic virus type 1 (HTLV-1) infection is a neglected disease despite roughly 15 million people are chronically infected worldwide. Lifelong less than 10% of carriers develop life-threatening diseases, mostly a subacute myelopathy known as tropical spastic paraparesis (TSP) and a lymphoproliferative disorder named adult T-cell leukemia (ATL). HTLV-1 is efficiently transmitted perinatally (breastfeeding), sexually (more from men to women) and parenterally (transfusions, injection drug user (IDU), and transplants). To date there is neither prophylactic vaccine nor effective antiviral therapy. A total of 327 cases of HTLV-1 infection had been reported at the HTLV-1 Spanish registry until December 2016, of whom 34 had been diagnosed with TSP and 25 with ATL. Overall 62% were Latin American immigrants and 13% were persons of African origin. The incidence of HTLV-1 in Spain has remained stable for nearly a decade with 20–25 new cases yearly. Of the 21 newly diagnosed HTLV-1 cases during year 2016, one was a native Spaniard pregnant woman, and four presented with symptomatic disease, including three with ATL and one with TSP. Underdiagnosis of HTLV-1 in Spain must be high (iceberg model), which may account for the disproportionate high rate of symptomatic cases (almost 20%) and the late recognition of preventable HTLV-1 transmissions in special populations, such as newborns and transplant recipients. Our current estimate is of 10 000 persons living with HTLV-1 infection in Spain. Given the large flux of immigrants and visitors from HTLV-1 endemic regions to Spain, the expansion of HTLV-1 screening policies is warranted. At this time, it seems worth recommending HTLV testing to all donor/recipient organ transplants and pregnant women regardless place of birth. Although current leukoreduction procedures largely prevent HTLV-1 transmission by blood transfusions, HTLV testing of all first-time donors should be cost-effective contributing to unveil asymptomatic unaware HTLV-1 carriers., The work was funded in part by grants from F-IES and ISCIII-Fondos Feder (PI13/01574; ICI14/00372; CD14/0243; FI14/0264; CM13/0309; CES12/003).

Background A change of aspartic acid (D) to glycine (G) at position 222 in the haemagglutinin (HA) protein of pandemic influenza A (H1N1) 2009 viruses was described in Norway on November 2009 with considerable frequency in fatal and severe cases. This change was detected in other countries and was related only with severe disease. Other substitutions to glutamic acid (E) or asparagine (N) at position 222 were detected among pandemic viruses but it is unclear what implications might have in terms of severity. Objectives To analyse the appearance of amino acid substitutions at position 222 in the HA protein of circulating viruses in Spain and to determine their relationships with the disease symptoms observed. Study design Pandemic influenza A (H1N1) 2009 viruses detected in respiratory samples of 273 severe and 533 non-severe cases from different Spanish regions were selected for sequencing of a partial segment of HA1 subunit and studied to monitor substitutions at position 222. Results D222G substitution was only detected in viruses from 14 severe cases (5.12%). D222E was found in viruses from 47 severe (17.21%) and from 52 non-severe cases (9.75%). D222N occurred in viruses from 3 additional severe cases (0.37%). Conclusion Appearance of D222G and D222E substitution in HA of pandemic influenza A (H1N1) viruses circulating in Spain might be related with severe respiratory disease.

Human parechoviruses (HPeV) have been recently recognized as important viral agents in paediatric infections. The aims of this study were to investigate the HPeV infection prevalence in infants