Intervirology最新文献

Background: Transmission of many viruses occurs by direct transmission during a close contact between two hosts, or by an indirect transmission through the environment. Several and often interconnected factors, both abiotic and biotic, determine the persistence of these viruses released in the environment, which can last from a few seconds to several years. Moreover, viruses in the environment are able to travel short to very long distances, especially in the air or in water.

Summary: Although well described now, the role of these environments as intermediaries or as reservoirs in virus transmission has been extensively studied and debated in the last century. The majority of these discoveries, such as the pioneer work on bacteria transmission, the progressive discoveries of viruses, as well as the persistence of the influenza virus in the air varying along with droplet sizes, or the role of water in the transmission of poliovirus, have contributed to the improvement of public health. Recent outbreaks of human coronavirus, influenza virus, and Ebola virus have also demonstrated the contemporaneity of these research studies and the need to study virus persistence in the environment. Key Messages: In this review, we discuss historical discoveries that contributed to describe biotic and abiotic factors determining viral persistence in the environment.

Background: The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its disease CO-VID-19 has strongly encouraged the search for antiviral compounds. Most of the evaluated drugs against SARS-CoV-2 derive from drug repurposing of Food and Drug Administration-approved molecules. These drugs have as target three major processes: (1) early stages of virus-cell interaction, (2) viral proteases, and (3) the viral RNA-dependent RNA polymerase.

Summary: This review focused on the basic principles of virology and pharmacology to understand the importance of early stages of virus-cell interaction as therapeutic targets and other main processes vital for SARS-CoV-2 replication. Furthermore, we focused on describing the main targets associated with SARS-CoV-2 antiviral therapy and the rationale of drug combinations for efficiently suppressing viral replication. Key Messages: We hypothesized that blocking of both entry mechanisms could allow a more effective antiviral effect compared to the partial results obtained with chloroquine or its derivatives alone. This approach, already used to achieve an antiviral effect higher than that offered by every single drug administered separately, has been successfully applied in several viral infections such as HIV and HCV. This review will contribute to expanding the perception of the possible therapeutic targets in SARS-CoV-2 infection and highlight the benefits of using combination therapies.

Background: Dengue fever is one of the most common human arbovirus infections worldwide. In Pakistan, dengue initially became endemic in the big cities and then expanded to remote areas of the country. The current study reports the dengue epidemics, anti-DENV antibodies prevalence during the active and post-dengue infection, risk factors, disease symptoms, and spotting dengue infection densities in district Swat of Pakistan.

Methods: Clinical signs and demographic data of dengue suspected individuals were collected at the time of screening through non-structural protein-1 antigen detection test during 2013-2015. Moreover, selected dengue confirmed individuals were screened for the presence of anti-dengue immunoglobulin (Ig) M and G during the active infection period and post-dengue infection.

Results: A total of 8,770 individuals were infected with dengue in 2013 with 36 (0.41%) case fatalities, 307 in 2014 with no case fatality, and 13 in 2015 with no case fatality. The number of male and female cases were 6,139 and 2,631 in 2013, 183 and 124 in 2014, and only 10 and 3 in 2015, respectively. Among all the localities, Tehsil Babozai, an urban setting, reported the highest number of dengue patients during all the study years, that is, 7,673 (87.49% of the total cases) in 2013, 294 (95.76% of the total cases) in 2014, and 13 (100% cases) in 2015. Among 6 age groups, 21-30 years was found to be highly infected in 2013 (37.13% of all cases) and 2014 (33.55%). Furthermore, 1,231 (21.94% of all cases) had IgM antibodies and 71 (1.26%) had IgG antibodies in 2013, 78 (26% of all cases) had IgM antibodies and 7 (2.33%) had IgG antibodies in 2014, and only 4 (30.76%) patients had IgM and 0 (0%) had IgG antibodies in 2015. Furthermore, urban areas had the highest infection density in district Swat. The majority of the patients in rural areas had a traveling history to the urban areas before their illness.

Conclusion: To sum up, male gender, young individuals, and those living in urban areas were at the greater risk of dengue infection.

Hepatitis E virus (HEV), a major etiologic agent of enterically transmitted hepatitis worldwide, is known to cause outbreaks. Diagnosis of the causative agent is important for patient management, understanding epidemiology and outbreak mitigation. We attempted to develop an algorithm for molecular diagnosis and compared the diagnostic accuracy of 2 of HEV IgM ELISA tests during an outbreak. Eighty-four blood samples collected during an outbreak in central India were referred to a nodal laboratory for confirmation of diagnosis. The samples were tested by serological and molecular testes. The results were analyzed by statistical tests. Both the IgM ELISAs were equally competent to diagnose HEV infection when samples were collected after 7.95 ± 3.2 days of onset of illness, whereas nRT-PCR proved a better test when samples were collected between 0 and 6.17 ± 1.97 days of illness. During HEV outbreaks, it is not possible to test all suspected cases by both serological and molecular tests; we suggest testing all ELISA-negative and samples collected in early phase (<7 days) of illness by molecular tests to rule out false-negative results. More studies with large sample size will aid in designing national guidelines for molecular diagnosis of HEV.

Background: Antibody-dependent enhancement (ADE) of dengue virus (DENV) infection is identified as the main risk factor of severe dengue diseases. The underlying mechanisms leading to severe dengue fever remain unclear.

Methods: THP-1 cells were treated with an autophagy inducer (rapamycin) or inhibitor (3-methyladenine [3-MA]) and infected with DENV and DENV-ADE. In order to investigate the expression profile of autophagy-related genes in DENV-ADE and DENV direct infection of THP-1 cells, the PCR array including 84 autophagy-related genes was selected to detect the expression of related genes, and then heat map and clustergram were established by analysis software to compare the expression differences of these genes between the DENV-ADE and DENV direct infection.

Results: Autophagy-inducing complex related genes ATG5 and ATG12 were upregulated, and autophagosomes were also observed by transmission electron microscopy among DENV-ADE- and DENV-infected THP-1 cells, which indicated that autophagy was involved in dengue infection. The results show that 3-MA has a significant inhibitory effect on ATG12 in THP-1 cells; on the contrary, the expression of ATG12 was upreg-ulated in THP-1 cells that were treated with rapamycin. The autophagy-related genes ESR1, INS, BNIP3, FAS, TGM2, ATG9B, and DAPK1 exhibited significant differences between DENV-ADE and DENV direct infection groups.

Conclusion: In the present study, an additional mechanism of autophagy was inhibited by the autophagy inhibitor (3-MA) in DENV- and DENV-ADE-infected THP-1 cells. Our finding provided a clear link between autophagy and antibody-enhanced infection of DENV.

Background: This study was planned to investigate the association betweenhuman cytomegalovirus (HCMV) infection and gastrointestinal cancer (GIC) risk, by undertaking a meta-analysis and case-control cross-sectional study.

Summary: A cross-sectional study analysis of 160 GIC patients and 100 control subjects indicated significantly higher HCMV prevalence in GIC patients based on the HCMV IgM test. However, a similar analysis based on an IgG test revealed no significant relationship. Further meta-analysis of 11 studies, including 1,044 patients and 991 healthy subjects, displayed HCMV infection as an important risk factor for not only colorectal cancer occurrence and development based on a HCMV DNA test, but also for GIC based on a HCMV IgM test. However, the IgG test again displayed no significant relationship between HCMV infection and GIC occurrence. Key Message: Overall, our study revealed that HCMV infection is associated with an increased GIC risk. However, additional studies are warranted to elucidate the molecular mechanism underlying this association.