Molecular and biological characterization of hepatitis B virus subgenotype F1b clusters: Unraveling its role in hepatocarcinogenesis.

Hepatitis B virus (HBV) subgenotype F1b infection has been associated with the early occurrence of hepatocellular carcinoma in chronically infected patients from Alaska and Peru. In Argentina, however, despite the high prevalence of subgenotype F1b infection, this relationship has not been described. To unravel the observed differences in the progression of the infection, an in-depth molecular and biological characterization of the subgenotype F1b was performed. Phylogenetic analysis of subgenotype F1b full-length genomes revealed the existence of two highly supported clusters. One of the clusters, designated as gtF1b Basal included sequences mostly from Alaska, Peru and Chile, while the other, called gtF1b Cosmopolitan, contained samples mainly from Argentina and Chile. The clusters were characterized by a differential signature pattern of eight nucleotides distributed throughout the genome. In vitro characterization of representative clones from each cluster revealed major differences in viral RNA levels, virion secretion, antigen expression levels, as well as in the localization of the antigens. Interestingly, a differential regulation in the expression of genes associated with tumorigenesis was also identified. In conclusion, this study provides new insights into the molecular and biological characteristics of the subgenotype F1b clusters and contributes to unravel the different clinical outcomes of subgenotype F1b chronic infections.

Viruela símica: zoonosis emergente con impacto global / Monkeypox: emerging zoonosis with unprecedentedglobal impact

El virus de la viruela símica es un orthopoxvirus de características zoonóticas endémico en las regiones de África Central y África Occidental, donde causa brotes desde 1970. En las últimas décadas se registró un aumento exponencial de casos, probablemente asociado a la disminución en la inmunidad conferida por la vacuna antivariólica, discontinuada luego de la erradicación de la viruela. En los últimos años se registraron casos esporádicos fuera del continente africano, siempre relacionados epidemiológicamente a la permanencia en áreas endémicas o contacto con animales infectados. Desde el 13 de mayo de 2022 se encuentra en curso el mayor brote de viruela símica registrado fuera de las áreas endémicas de África, con casos en los cinco continentes. La extensión, el impacto y la duración del brote permanecen aún inciertos.

Monkeypox virus is an orthopoxvirus with zoonotic characteristics endemic in Central and West Africa regions, where it has caused outbreaks since 1970. An exponential increase in cases has been registered in the last decades, probably associated with a decrease in the immunity conferred by the smallpox vaccine, discontinued after smallpox eradication. In recent years, sporadic cases have been reported outside the African continent, always epidemiologically related to permanence in endemic areas or contact with infected animals. Since May 13, 2022, the largest monkeypox outbreak ever reported outside Africa endemic areas, with cases on the five continents, is unfolding. The extent, impact and duration of this outbreak still remain uncertain

Infecciones fúngicas en pacientes con COVID-19 / Fungal infections in patients with COVID-19

En diciembre de 2019 se identificó en Wuhan, China, un nuevo coronavirus denominado SARS-CoV-2, agente causal de la epidemia de neumonía atípica COVID-2019, que el 11 de marzo de 2020 fue declarada pandemia por la OMS.Hasta el 30 de septiembre de 2020, en Argentina fueron confirmados 751.001 casos y más de 16.937 muertes.La frecuencia y el impacto de las coinfecciones que afectan a los pacientes infectados por SARS-Cov-2 se ha estudiado junto con el avance de la pandemia. Entre las debidas a hongos se encuentran las fungemias por Candida sp, la aspergilosis invasora, las micosis sistémicas endémicas y la neumocistosis. Presentamos las distintas coinfecciones micosis-COVID-19 que fueron asistidas en nuestra institución entre abril y septiembre de 2020, y se realiza un análisis de las características de estas infecciones en pacientes con y sin sida. En este período se internaron 2837 pacientes, 2287 tuvieron diagnóstico confirmado de COVID-19. La coinfección de COVID-19 con micosis pulmonares o sistémicas fue menor al 1%.Dieciocho pacientes presentaron infecciones fúngicas pulmonares o sistémicas. Ocho padecieron candidemias, cinco criptococosis meningeas, dos histoplasmosis, dos aspergilosis invasoras agudas probables y una aspergilosis pulmonar crónica. La estadía prolongada en terapia intensiva facilitó las fungemias por Candida sp, los casos de histoplasmosis y criptococosis parecen relacionarse con la enfermedad avanzada por VIH y no con COVID-19. Los enfermos con un componente inflamatorio basal alto con neumonía grave por coronavirus se relacionan más con micosis invasoras que los enfermos VIH positivos con niveles bajos de LTCD4+

On December 2019 a new coronavirus (SARS-CoV2) result in atypical pneumonía epidemic, it was identified in Wuhan China and it was called COVID-19. Then on March 11 was declared pandemic by the WHO.Until September 30, 2020 in Argentina 751,001 cases and more than 16,937 deaths have been confirmed. The frequency and impact of co-infections affecting SARS-Cov2 infected patients has been studied with the advance of the pandemic. Among those due to fungi are Candida sp fungemias, invasive aspergillosis, endemic systemic mycoses, and pneumocystosis.We present the different mycosis-COVID-19 co-infections that were assisted in F. J. Muñiz Hospital between April and September of this year and review the characteristics of these infections in patients with and without AIDS is carried out.In this period, 2,837 patients were admitted in the Muñiz hospital, 2,287 had a confirmed diagnosis of COVID-19.Co-infection of COVID-19 with pulmonary or systemic mycoses was less than 1%.Eighteen patients had pulmonary or systemic fungal infections. Eight suffered from candidemia, five meningeal cryptococcosis, two histoplasmosis, two probable acute invasive aspergillosis, and one chronic pulmonary aspergillosis.Prolonged stay in intensive care facilitated fungemia due to Candida sp. Histoplasmosis and cryptococcosis cases seem to be related to advanced HIV disease and not to COVID-19.Patients with a high baseline inflammatory component with severe coronavirus pneumonia are more associated with invasive mycoses than HIV-positive patients with low levels of LTCD4 +

Molecular characterization of hepatitis B virus X gene in chronic hepatitis B patients.

BACKGROUND: HBV-X protein is associated with the pathogenesis of HBV related diseases, specially in hepatocellular carcinomas of chronic patients. Genetic variability of the X gene includes genotypic specific variations and mutations emerging during chronic infection. Its coding sequence overlaps important regions for virus replication, including the basal core promoter. Differences in the X gene may have implications in biological functions of the protein and thus, affect the evolution of the disease. There are controversial results about the consequences of mutations in this region and their relationship with pathogenesis. The purpose of this work was to describe the diversity of HBV-X gene in chronic hepatitis patients infected with different genotypes, according to liver disease. METHODS: HBV-X gene was sequenced from chronic hepatitis B patient samples, analyzed by phylogeny and genotyped. Nucleotide and aminoacid diversity was determined calculating intragenetic distances. Mutations at 127, 130 and 131 aminoacids were considered in relation to liver disease. RESULTS: The most prevalent genotype detected in this cohort was F (F1 and F4), followed by D and A. Most of the samples corresponding to genotypes A and F1 were HBeAg(+) and for genotypes D and F4, HBeAg(-) samples were represented in a higher percentage. Intragenetic distance values were higher in HBeAg(-) than in positive samples for all genotypes, and lower in overlapped regions, compared to single codification ones. Nucleotide and aminoacid diversities were higher in HBeAg(-), than in HBeAg(+) samples. CONCLUSIONS: Independently of the infecting genotypes, mutations at any of 127, 130 and/or 131 aminoacid positions and HBeAg(-) status were associated with mild liver disease in this cohort.

Human herpesvirus 6: report of emerging pathogen in five patients with HIV/AIDS and review of the literature.

The reactivation of human herpesvirus 6 (HHV-6) in patients with AIDS can result in an acute and severe diffuse meningoencephalitis. We describe the epidemiological, clinical and outcome findings of five patients with diagnosis of HIV/AIDS and central nervous system involvement (CNS) due to HHV-6. Fever was present in all the patients. Meningeal compromise, seizures and encephalitis were present in some of the patients. Polymerase chain reaction (PCR) of cerebrospinal fluid (CSF) specimens was positive for HHV-6 in all the patients. HHV-6 should be included among opportunistic and emerging pathogens that involve the CNS in patients with AIDS.

Human herpesvirus 6: report of emerging pathogen in five patients with HIV/AIDS and review of the literature / Herpes virus humano 6: relato de patógenos emergentes em cinco pacientes com HIV/AIDS e revisão da literatura

The reactivation of human herpesvirus 6 (HHV-6) in patients with AIDS can result in an acute and severe diffuse meningoencephalitis. We describe the epidemiological, clinical and outcome findings of five patients with diagnosis of HIV/AIDS and central nervous system involvement (CNS) due to HHV-6. Fever was present in all the patients. Meningeal compromise, seizures and encephalitis were present in some of the patients. Polymerase chain reaction (PCR) of cerebrospinal fluid (CSF) specimens was positive for HHV-6 in all the patients. HHV-6 should be included among opportunistic and emerging pathogens that involve the CNS in patients with AIDS.

A reativação do herpesvírus humano 6 (HHV-6), em um hospedeiro com AIDS, pode resultar em meningoencefalite aguda difusa. Nós descrevemos a epidemiologia, a clínica e resultados encontrados em cinco pacientes com diagnóstico de HIV/AIDS e comprometimento do sistema nervoso central (SNC) devido ao HHV-6. Todos os pacientes apresentaram febre. Sinais e sintomas de comprometimento meníngeo, convulsões e encefalite podem ser encontrados. A reação em cadeia da polimerase (PCR) de amostras do líquor foi positiva para HHV-6 em todos os pacientes. O HHV-6 deve ser incluído entre os patógenos emergentes oportunistas que comprometem o SNC de pacientes com AIDS.

Characterization of the basal core promoter and precore regions in anti-HBe-positive inactive carriers of hepatitis B virus.

BACKGROUND: The study of hepatitis B virus (HBV) genomic heterogeneity has become a major issue in investigations aimed at understanding the relationship between HBV mutants and the wide spectrum of clinical and pathological conditions associated with HBV infection. Although most chronically infected HBV patients are inactive carriers, several virological aspects of this state remain unclear. METHODS: In order to determine the prevalence and clinical significance of mutations in the basal core promoter (BCP) and precore (pC) regions among inactive carriers, the nucleotide sequences from 41 inactive carriers were analyzed and compared with those from 29 individuals with chronic active hepatitis. RESULTS: Genotypes A (24.3%), D (37.1%), F1b (12.9%), and F4 (18.6%) were the most prevalent. Mutations in the BCP/pC regions were observed in most of the inactive carriers (92.7%) and in most of the patients with chronic active hepatitis (93.1%). The prevalence of mutation 1764(A) was significantly higher in patients with chronic active hepatitis (65.5%) than in inactive carriers (36.6%) (p=0.038), whereas the prevalences of mutations at the other positions analyzed were not significantly different. Older patients (>50 years) showed BCP/pC patterns with a higher number of substitutions. Mutations were found to be biased by genotype: the 1896(A) mutation was highly prevalent in genotypes D and F4, while alternative substitutions in the pC region were more prevalent in genotypes A and F1b. CONCLUSIONS: Mutations in the BCP/pC regions are the hallmark of chronic anti-HBe-positive individuals; nevertheless, the even distribution of mutations in active and inactive carriers suggests that BCP/pC mutations may occur during HBV infection not strictly related to the HBV infection activity.

[Acute necrotizing myelitis in an AIDS patient]. / Mielitis aguda necrotizante en un paciente con SIDA.

In the setting of HIV infection, cytomegalovirus (CMV) and herpes simplex virus type 1-2 (HSV 1-2) can affect both the central and peripheral nervous systems. These agents can involve the spinal cord and produce a necrotizing transverse myelitis. This usually occurs in AIDS patients with severe immunodeficiency: CD4+ lymphocyte counts typically are less than 50 cell/microL. The clinical presentation, CSF and imaging studies can provide a high level of suspicion diagnosis. Prompt initiation of antiviral specific drugs is essential. We report a patient with an acute necrotizing myelitis (cauda equina syndrome) secondary to CMV and HSV infections.

Mielitis aguda necrotizante en un paciente con SIDA. / [Acute necrotizing myelitis in an AIDS patient]

In the setting of HIV infection, cytomegalovirus (CMV) and herpes simplex virus type 1-2 (HSV 1-2) can affect both the central and peripheral nervous systems. These agents can involve the spinal cord and produce a necrotizing transverse myelitis. This usually occurs in AIDS patients with severe immunodeficiency: CD4+ lymphocyte counts typically are less than 50 cell/microL. The clinical presentation, CSF and imaging studies can provide a high level of suspicion diagnosis. Prompt initiation of antiviral specific drugs is essential. We report a patient with an acute necrotizing myelitis (cauda equina syndrome) secondary to CMV and HSV infections.

Mielitis aguda necrotizante en un paciente con SIDA / Acute necrotizing myelitis in an AIDS patient

In the setting of HIV infection, cytomegalovirus (CMV) and herpes simplex virus type 1-2 (HSV 1-2) can affect both the central and peripheral nervous systems. These agents can involve the spinal cord and produce a necrotizing transverse myelitis. This usually occurs in AIDS patients with severe immunodeficiency: CD4+ lymphocyte counts typically are less than 50 cell/microL. The clinical presentation, CSF and imaging studies can provide a high level of suspicion diagnosis. Prompt initiation of antiviral specific drugs is essential. We report a patient with an acute necrotizing myelitis (cauda equina syndrome) secondary to CMV and HSV infections (AU)

Mielitis aguda necrotizante en un paciente con SIDA / Acute necrotizing myelitis in an AIDS patient

In the setting of HIV infection, cytomegalovirus (CMV) and herpes simplex virus type 1-2 (HSV 1-2) can affect both the central and peripheral nervous systems. These agents can involve the spinal cord and produce a necrotizing transverse myelitis. This usually occurs in AIDS patients with severe immunodeficiency: CD4+ lymphocyte counts typically are less than 50 cell/microL. The clinical presentation, CSF and imaging studies can provide a high level of suspicion diagnosis. Prompt initiation of antiviral specific drugs is essential. We report a patient with an acute necrotizing myelitis (cauda equina syndrome) secondary to CMV and HSV infections

Virus y linfoma: leucemia / Virus and lymphoma: leukemia

El virus HTLV-I fue encontrado promotor de la Leucemia T del adulto y de la paraparesia espástica tropical. No es el único virus inculpado con la producción de neoplasias en el hombre. Se trata de un virus muy similar al HTLV-II o HIV, que se propaga en forma muy similar a éste. Tiene como diferencia fundamental, al producción de atipías linfoides y su muy largo período de incubación. Se lo encuentra en casi todo el mundo, pero su origen es el sur del Japón, si bien es endémico en la costa Americana del Pacífico, donde produce el cuadro neurológico mencionado anteriormente

Virus y linfoma: leucemia / Virus and lymphoma: leukemia

El virus HTLV-I fue encontrado promotor de la Leucemia T del adulto y de la paraparesia espástica tropical. No es el único virus inculpado con la producción de neoplasias en el hombre. Se trata de un virus muy similar al HTLV-II o HIV, que se propaga en forma muy similar a éste. Tiene como diferencia fundamental, al producción de atipías linfoides y su muy largo período de incubación. Se lo encuentra en casi todo el mundo, pero su origen es el sur del Japón, si bien es endémico en la costa Americana del Pacífico, donde produce el cuadro neurológico mencionado anteriormente (AU)