{"id":2863,"date":"2020-11-12T12:58:37","date_gmt":"2020-11-12T17:58:37","guid":{"rendered":"https:\/\/med.virginia.edu\/bims\/?p=2863"},"modified":"2020-11-12T12:58:37","modified_gmt":"2020-11-12T17:58:37","slug":"uva-unveils-how-hiv-begins-to-invade-our-cells","status":"publish","type":"post","link":"https:\/\/med.virginia.edu\/bims\/uva-unveils-how-hiv-begins-to-invade-our-cells\/","title":{"rendered":"UVA Unveils How HIV Begins to Invade Our Cells"},"content":{"rendered":"

\"amandaScientists at the University of Virginia School of Medicine<\/a><\/strong>\u00a0have developed a method to understand how HIV and other viruses first begin to infect our cells, and that could help us prevent COVID-19 and other diseases.<\/p>\n

Such viruses are so small that scientists must study them using electron microscopes, rather than traditional light microscopes. But limitations in how samples are prepared for electron microscopy have long stymied efforts to understand the very beginning of the infection process. Basically, scientists have gone into battle unable to see how the invasion starts.<\/p>\n

UVA researchers, however, have devised an ingenious solution. They have used tiny, detached portions of a cell\u2019s membrane to witness how HIV and other viruses first launch their assaults. The delicate virus-cell membrane samples are super-rapidly frozen while the virus is trying to breach the cell membrane to form \u201cvitreous\u201d (glassy, non-crystalline) ice, so the structures can be preserved as in solution and imaged at minus-196degrees Celsius using cryo-electron microscopy, a technique that was\u00a0awarded the Nobel Prize in Chemistry in 2017<\/a><\/strong>.<\/p>\n

\u201cSamples for electron microscopy need to be extremely thin \u2013 thinner than a single human cell \u2013 which previously made imaging viruses as they begin infection by entering a cell very difficult to nearly impossible, depending on the virus,\u201d UVA researcher Amanda E. Ward said. \u201cVisualizing intermediate steps as the viral and plasma membranes fuse brings us closer to a molecular-level understanding of the dramatic rearrangements that proteins and lipids undergo as two membranes become one and a virus begins its infectious cycle.\u201d<\/p>\n

Stopping Viral Infections<\/strong><\/h3>\n

The UVA researchers call their little membrane sections \u201cblebs.\u201d They have tested their approach with HIV, but say it could be used to better understand many other viruses, including SARS-CoV-2, which causes COVID-19. Scientists just would need to produce the blebs from different cells, such as lung epithelial cells for SARS-CoV-2, that express the appropriate receptors for the virus they wish to study.<\/p>\n

The new technique has already allowed the UVA researchers to better understand how HIV enters our cells and how that process can be disrupted by two proteins our bodies make, Serinc3 and Serinc5.<\/p>\n

\u201cPractically every living thing can be infected by viruses, so organisms have evolved a myriad of ways to prevent viral infection and damage,\u201d Ward explained. \u201cSome of the most recently identified restriction factors, Serinc3 and Serinc5, can block HIV and other lentiviruses from entering cells, although HIV has evolved a way to counteract Serincs\u2019 inhibition, so they may not play a large role in controlling HIV infection in humans.\u201d<\/p>\n

Scientists, however, may be able to improve on what nature created. They could enhance that same mechanism, for example, to create drugs that would block the infection process.<\/p>\n

The new tool has already yielded important insights into how our bodies respond to HIV infections. The scientists determined, for example, that the Serinc proteins seek to stop HIV by causing broad changes to the membrane fusion process. This came as a surprise, defying\u00a0the previous scientific understanding of Serincs and other restriction factors like them.<\/p>\n

\u201cOur methods are quite general, and many human viruses share lots of common principles when entering cells. Therefore, we expect to learn much more about the fundamentals of cell entry of many viruses and how to inhibit that process,\u201d said lead researcher Lukas K. Tamm, who chairs UVA\u2019s Department of\u00a0Molecular Physiology and Biological Physics. \u201cWe are lucky to be particularly well-equipped at UVA for these kinds of studies, and we benefit from a fantastic group of exquisite researchers, physicians and trainees contributing their expertise in this area. We are also fortunate to have been funded by the NIH for research on virus entry continuously for nearly 30 years.\u201d<\/p>\n

Findings Published<\/strong>\u00a0<\/b><\/h3>\n

The researchers have\u00a0published their findings in the Journal of Biological Chemistry<\/a><\/strong>. The article was selected as the issue\u2019s cover story, with the cover featuring imagery by Ward and\u00a0fellow UVA Medical Science Training Program student Jocelyn Ray. The research team consisted of Ward, Volker Kiessling, Owen Pornillos, Judith M. White, Barbie K. Ganser-Pornillos and Tamm.<\/p>\n

The work was supported by the National Institutes of Health, grants R01 AI030557, F30 HD101348, R01\u00a0AI114776\u00a0and P50 AI150464.\u00a0<\/i><\/p>\n

This story by Josh Barney originally appeared in UVA Today<\/a> on November 6, 2020. Photo courtesy of UVA Health.\u00a0<\/em><\/p>\n","protected":false},"excerpt":{"rendered":"

Scientists at the University of Virginia School of Medicine\u00a0have developed a method to understand how HIV and other viruses first begin to infect our cells, and that could help us prevent COVID-19 and other diseases. Such viruses are so small that scientists must study them using electron microscopes, rather than traditional light microscopes. But limitations […]<\/p>\n","protected":false},"author":1,"featured_media":2864,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"inline_featured_image":false,"footnotes":"","_links_to":"","_links_to_target":""},"categories":[4],"tags":[],"class_list":["post-2863","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-research-highlights"],"acf":false,"yoast_head":"\nUVA Unveils How HIV Begins to Invade Our Cells - Biomedical Sciences Graduate Program<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/med.virginia.edu\/bims\/uva-unveils-how-hiv-begins-to-invade-our-cells\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"UVA Unveils How HIV Begins to Invade Our Cells - Biomedical Sciences Graduate Program\" \/>\n<meta property=\"og:description\" content=\"Scientists at the University of Virginia School of Medicine\u00a0have developed a method to understand how HIV and other viruses first begin to infect our cells, and that could help us prevent COVID-19 and other diseases. 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