Intervirology最新文献

{"title":"Understanding Severe Acute Respiratory Syndrome Coronavirus 2 Replication to Design Efficient Drug Combination Therapies.","authors":"Joseph T Ortega, Jose L Zambrano, Beata Jastrzebska, Ferdinando Liprandi, Hector R Rangel, Flor H Pujol","doi":"10.1159/000512141","DOIUrl":"10.1159/000512141","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Summary: </strong>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.</p>","PeriodicalId":14547,"journal":{"name":"Intervirology","volume":"63 1-6","pages":"2-9"},"PeriodicalIF":4.6,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000512141","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38528096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Comprehensive Study of Dengue Epidemics and Persistence of Anti-Dengue Virus Antibodies in District Swat, Pakistan.","authors":"Naveed Ahmad,&nbsp;Tariq Khan,&nbsp;Syed Muhammad Jamal","doi":"10.1159/000510347","DOIUrl":"https://doi.org/10.1159/000510347","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>To sum up, male gender, young individuals, and those living in urban areas were at the greater risk of dengue infection.</p>","PeriodicalId":14547,"journal":{"name":"Intervirology","volume":"63 1-6","pages":"46-56"},"PeriodicalIF":4.6,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000510347","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38487252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proposed Algorithm for Hepatitis E Virus Diagnosis in the Early Phase of Illness.","authors":"Sulekha Yadav,&nbsp;Rekha Barapatre,&nbsp;Ravendra Sharma,&nbsp;Arvind Neral,&nbsp;Pradip Barde","doi":"10.1159/000510725","DOIUrl":"https://doi.org/10.1159/000510725","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":14547,"journal":{"name":"Intervirology","volume":"63 1-6","pages":"66-70"},"PeriodicalIF":4.6,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000510725","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38459999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of Autophagy-Mediated Dengue Virus Antibody-Dependent Enhancement Infection of THP-1 Cells.","authors":"Liming Jiang,&nbsp;Qiangming Sun","doi":"10.1159/000511420","DOIUrl":"https://doi.org/10.1159/000511420","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":14547,"journal":{"name":"Intervirology","volume":"63 1-6","pages":"57-65"},"PeriodicalIF":4.6,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000511420","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38615311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cytomegalovirus Infection Is a Risk Factor in Gastrointestinal Cancer: A Cross-Sectional and Meta-Analysis Study.","authors":"Ya-Li Lv,&nbsp;Fei-Fei Han,&nbsp;Zhuo-Ling An,&nbsp;Yangjie Jia,&nbsp;Ling-Ling Xuan,&nbsp;Li-Li Gong,&nbsp;Wen Zhang,&nbsp;Lu-Lu Ren,&nbsp;Song Yang,&nbsp;He Liu,&nbsp;Li-Hong Liu","doi":"10.1159/000506683","DOIUrl":"https://doi.org/10.1159/000506683","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Summary: </strong>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.</p>","PeriodicalId":14547,"journal":{"name":"Intervirology","volume":"63 1-6","pages":"10-16"},"PeriodicalIF":4.6,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000506683","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38246002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical, Virological, and Immunological Profiles of DENV, ZIKV, and/or CHIKV-Infected Brazilian Patients.","authors":"Juan Camilo Sánchez-Arcila,&nbsp;Jessica Badolato-Correa,&nbsp;Thiara Manuele Alves de Souza,&nbsp;Iury Amâncio Paiva,&nbsp;Luciana Santos Barbosa,&nbsp;Priscila Conrado Guerra Nunes,&nbsp;Monique da Rocha Queiroz Lima,&nbsp;Flavia Barrento Dos Santos,&nbsp;Paulo Vieira Damasco,&nbsp;Rivaldo Venancio da Cunha,&nbsp;Elzinandes Leal de Azeredo,&nbsp;Luzia Maria de Oliveira-Pinto","doi":"10.1159/000510223","DOIUrl":"https://doi.org/10.1159/000510223","url":null,"abstract":"Background: Arboviruses co-circulating within a population that are transmitted by the same vector have the potential to cause coinfections. Coinfections with dengue virus (DENV), Zika virus (ZIKV), and chikungunya virus (CHIKV) have been occurring in Brazil, but it is not well-understood how human responses vary during mono- or coinfections and whether they play different roles in pathogenesis. Methods: We investigated the clinical, virological, and immunological status during patients’ acute infections, focusing on the CCL/CXC chemokines, proinflammatory, as well as anti-inflammatory cytokines levels quantified by ELISAs. Viral load was determined by qRT-PCR in serum samples from 116 acute DENV, ZIKV, CHIKV, DENV/ZIKV, and CHIKV/ZIKV-infected adult patients from Brazil. Results: Most of the acute patients displayed fever, headache, prostration, and myalgia, regardless of the type of arbovirus infection. Zika viral load was higher in CHIKV/ZIKV coinfected patients compared with ZIKV or DENV/ZIKV infections. All infected individuals presented increased concentrations of C-X-C motif chemokine ligand 10/interferon protein-10 (CXCL10/IP-10), C-C motif chemokine ligand 2/monocyte chemoattractant protein-1 (CCL2/MCP-1), and tumor necrosis factor alpha (TNF-α) compared to healthy donors. Interestingly, the ZIKV group separated from CHIKV/ZIKV due to higher levels of interleukin-10 (IL-10) and lower levels of TNF-α. While DENV/ZIKV differentiated from CHIKV due to their higher levels of CCL2/MCP-1, in CHIKV- and CHIKV/ZIKV-infected patients, levels of CXC10/IP-10, CCL2/MCP-1, and migration inhibitory factor (MIF) were associated with CHIKV viral load. By contrast, in DENV/ZIKV- and CHIKV/ZIKV-infected patients, levels of CXCL10/IP-10, CCL2/MCP-1, and TNF-α showed a significant inverse correlation with ZIKV viral load. Conclusions: From all the circulating mediators measured, we detected differences of IL-10, TNF-α, and CCL2/MCP-1 between arbovirus groups. We hypothesize that CXC10/IP-10, CCL2/MCP-1, and MIF in the CHIKV-infected group could regulate the CHIKV viral load, while CXC10/IP-10, CCL2/MCP-1, and TNF-α in DENV/ZIKV, and CHIKV/ZIKV groups, could regulate ZIKV viral load.","PeriodicalId":14547,"journal":{"name":"Intervirology","volume":"63 1-6","pages":"33-45"},"PeriodicalIF":4.6,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000510223","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38413981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Influence of Antiretroviral Therapy on Hepatitis C Virus Viral Load and Liver Fibrosis in Human Immunodeficiency Virus-Coinfected Patients: An Observational Study","authors":"J. Soares, A. Ferreira, A. Silva-Pinto, F. Almeida, C. Piñeiro, R. Serrão, A. Sarmento","doi":"10.1159/000503631","DOIUrl":"https://doi.org/10.1159/000503631","url":null,"abstract":"Background: The role of antiretroviral therapy (ART) for Hepatitis C viral load (HCV-VL) and liver fibrosis is poorly understood. This study aimed at evaluating the influence of ART on HCV-VL and liver fibrosis in human immunodeficiency virus (HIV)/HCV-coinfected patients. Methods: We conducted a retrospective cohort study of HIV/HCV-coinfected patients followed at a tertiary university hospital. Results: In total, 143 patients were included. In 61 patients, ART initiation was accompanied by an increase in HCV-VL and a decrease in HIV viral load (HIV-VL), whereas ART suspension led to a decrease in HCV-VL and an increase in HIV-VL. Among the 55 HIV-suppressed patients who switched to a raltegravir (RAL)-containing regimen, median HCV-VL levels decreased significantly, while switching to a rilpivirine-containing regimen did not yield a significant reduction. Discussion: If the treatment of chronic hepatitis starts before ART, ART initiation should be delayed as much as possible. If ART has been started, it is advisable to wait 1 year before initiating chronic hepatitis treatment. RAL as the third agent in an ART regimen could be beneficial in HIV/HCV-coinfected patients, in comparison to other antiretroviral drugs. Conclusion: The start and the suspension of ART significantly interferes with HCV-VL in HIV/HCV-coinfected patients.","PeriodicalId":14547,"journal":{"name":"Intervirology","volume":"62 1","pages":"182 - 190"},"PeriodicalIF":4.6,"publicationDate":"2019-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000503631","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42655247","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Outbreak of Human Parainfluenza Virus 3 (Phylogenetic Subcluster C5) Infection among Adults at a Residential Care Facility for the Disabled in Croatia, 2018","authors":"R. Čivljak, T. Košutić-Gulija, A. Slović, Eva Huljev, N. Turčić, T. Meštrović, J. Vraneš, S. Ljubin-Sternak","doi":"10.1159/000503630","DOIUrl":"https://doi.org/10.1159/000503630","url":null,"abstract":"Introduction: Although highly pertinent for children, outbreaks of human parainfluenza virus (HPIV) may cause up to 15% of all respiratory illnesses in adults and predispose them to serious adverse outcomes, with HPIV serotype 3 (HPIV3) being the most common. This study represents the first report of an HPIV3 outbreak among adults at a long-term health-care facility in Croatia. Methods: A retrospective study was conducted to investigate an outbreak of acute respiratory infection (ARI) at a single residential care facility for the disabled in Croatia. Demographic, epidemiological, and clinical data were collected for all residents, while hospitalized patients were appraised in detail by laboratory/radiological methods. Multiplex PCR for respiratory viruses and sequencing was performed. Partial HPIV3 HN 581 nt sequences were aligned with HPIV3 sequences from the GenBank database to conduct a phylogenetic analysis, where different bioinformatic approaches were employed. Results: In late June 2018, 5 of the 10 units at the facility were affected by the outbreak. Among the 106 residents, 23 (21.7%) developed ARI, and 6 (26.1%) of them were hospitalized. HPIV3 was identified in 18 (73%) of the residents and 5 (83%) of the hospitalized individuals. Isolated HPIV3 strains were classified within the phylogenetic subcluster C5 but grouped on 2 separate branches of the phylogenetic tree. During the entire outbreak period, none of the institution’s employees reported symptoms of ARI. Conclusions: Our study has shown that this health care-associated outbreak of HPIV3 infection could have been linked to multiple importation events. Preventive measures in curbing such incidents should be enforced vigorously.","PeriodicalId":14547,"journal":{"name":"Intervirology","volume":"62 1","pages":"174 - 181"},"PeriodicalIF":4.6,"publicationDate":"2019-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000503630","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41414695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Front & Back Matter","authors":"","doi":"10.1159/000503839","DOIUrl":"https://doi.org/10.1159/000503839","url":null,"abstract":"","PeriodicalId":14547,"journal":{"name":"Intervirology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2019-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48139625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Primary HIV-1 Strains Use Nef To Downmodulate HLA-E Surface Expression.","authors":"Thomas van Stigt Thans, Janet I Akko, Annika Niehrs, Wilfredo F Garcia-Beltran, Laura Richert, Christina M Stürzel, Christopher T Ford, Hui Li, Christina Ochsenbauer, John C Kappes, Beatrice H Hahn, Frank Kirchhoff, Glòria Martrus, Daniel Sauter, Marcus Altfeld, Angelique Hölzemer","doi":"10.1128/JVI.00719-19","DOIUrl":"10.1128/JVI.00719-19","url":null,"abstract":"<p><p>Human immunodeficiency virus type 1 (HIV-1) has evolved elaborate ways to evade immune cell recognition, including downregulation of classical HLA class I (HLA-I) from the surfaces of infected cells. Recent evidence identified HLA-E, a nonclassical HLA-I, as an important part of the antiviral immune response to HIV-1. Changes in HLA-E surface levels and peptide presentation can prompt both CD8⁺ T-cell and natural killer (NK) cell responses to viral infections. Previous studies reported unchanged or increased HLA-E levels on HIV-1-infected cells. Here, we examined HLA-E surface levels following infection of CD4⁺ T cells with primary HIV-1 strains and observed that a subset downregulated HLA-E. Two primary strains of HIV-1 that induced the strongest reduction in surface HLA-E expression were chosen for further testing. Expression of single Nef or Vpu proteins in a T-cell line, as well as tail swap experiments exchanging the cytoplasmic tail of HLA-A2 with that of HLA-E, demonstrated that Nef modulated HLA-E surface levels and targeted the cytoplasmic tail of HLA-E. Furthermore, infection of primary CD4⁺ T cells with HIV-1 mutants showed that a lack of functional Nef (and Vpu to some extent) impaired HLA-E downmodulation. Taken together, the results of this study demonstrate for the first time that HIV-1 can downregulate HLA-E surface levels on infected primary CD4⁺ T cells, potentially rendering them less vulnerable to CD8⁺ T-cell recognition but at increased risk of NKG2A⁺ NK cell killing.<b>IMPORTANCE</b> For almost two decades, it was thought that HIV-1 selectively downregulated the highly expressed HLA-I molecules HLA-A and HLA-B from the cell surface in order to evade cytotoxic-T-cell recognition, while leaving HLA-C and HLA-E molecules unaltered. It was stipulated that HIV-1 infection thereby maintained inhibition of NK cells via inhibitory receptors that bind HLA-C and HLA-E. This concept was recently revised when a study showed that primary HIV-1 strains reduce HLA-C surface levels, whereas the cell line-adapted HIV-1 strain NL4-3 lacks this ability. Here, we demonstrate that infection with distinct primary HIV-1 strains results in significant downregulation of surface HLA-E levels. Given the increasing evidence for HLA-E as an important modulator of CD8⁺ T-cell and NKG2A⁺ NK cell functions, this finding has substantial implications for future immunomodulatory approaches aimed at harnessing cytotoxic cellular immunity against HIV.</p>","PeriodicalId":14547,"journal":{"name":"Intervirology","volume":"59 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2019-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1128/JVI.00719-19","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"63837986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}