| Abstract | HIV-1 član je porodice Retroviridae, a ujedno i jedan od najrasprostranjenijih lentivirusa današnjice s poprilično visokom godišnjom stopom prevalencije u svijetu. Kao rezultat zoonotskih prijenosa s primata postao je i humani patogen koji se prenosi preko tjelesnih tekućina, izazivajući u zaražene osobe imunodeficijenciju i narušavanje cjelokupnog zdravstvenog stanja. Izrazito velika mutabilnost HIV-1 genoma predstavlja i najveću prepreku njegovom iskorjenjivanju. Osnovnu građu sferičnog HIV-1 viriona čine ovojnica s ugrađenim šiljcima, kapsida i nukleoproteinski kompleks kojeg čine RNA i proteini važni za njegovu replikaciju. Klasificirano je ukupno 9 HIV-1 gena koji se, prema funkcijama, dijele u strukturne i pomoćne. Gag i env kodiraju proteine ovojnice i kapside, a pol enzimske proteine. Geni tat i rev zaslužni su za regulaciju genskog izražaja, dok vif, vpr, vpu i nef pospješuju virusnu imunopatogenezu. Nakon fuzije viriona s membranom domaćina, ulaska te reverzne transkripcije i integracije novosintetizirane DNA u genom domaćina, slijedi sinteza virusnih proteina i sklapanje novih virusnih čestica. Novonastali virioni potom pupaju, tj. izlaze iz stanice, čime započinje proces diseminacije. U obrani organizma od HIV-1 djeluje urođeni imunosni sustav (dendritičke i NK stanice, makrofagi te citokinska mreža), stečena imunost (CD4+ i CD8+ limfociti T i limfociti B), te tzv. intrinzični dio imunosnog sustava (APOBEC3G, TRIM5α, teterina i SAMHD1). Najvažniju ulogu u imunoevaziji virusa ima njegov pomoćni protein Nef koji, između ostalog, smanjuje izražaj MHC-I molekula (molekule glavnog sustava tkivne podudarnosti) usmjeravajući ih u razgradnju kako bi se izbjeglo razaranje zaraženih stanica od strane citotoksičnih limfocita T. Nef također potiče i aktivaciju transkripcijskih faktora, a time i replikaciju virusa. Ostali mehanizmi izbjegavanja imunosnog odgovora podrazumijevaju mutiranje ili maskiranje epitopa, latenciju, greške reverzne transkriptaze i dr. Zbog sve veće HIV-1 prilagodbe nužno je razviti što učinkovitiji lijek ili cjepivo kako bi se zaustavilo širenje ili poboljšala kvaliteta zaraženih. |
| Abstract (english) | HIV-1 belongs to the Retroviridae family and is one of the most widespread lentiviruses with a high annual prevalence rate. As a result of zoonotic transmission from primates, it has evolved into a human pathogen that is transmitted through body fluids and causes immunodeficiency and impaired general health in infected individuals. One of the main obstacles to viral eradication is the high mutation rate of the genome. The spherical HIV-1 virus consists of an envelope with built-in spikes, a capsid, and a nucleoprotein complex containing RNA molecules and proteins important for replication. A total of 9 genes have been classified, which are divided into structural and auxiliary genes according to their function. Gag and env code for envelope and capsid proteins, pol for enzyme proteins. The tat and rev genes are responsible for regulating gene expression, while vif, vpr, vpu, and nef promote viral immunopathogenesis. Infection of the host cell begins with fusion of the virion to the host membrane, entry, reverse transcription, and integration of the newly synthesized DNA into the host genome. After the synthesis of late viral proteins, including structural proteins, begins, new virions bud from the infected cell and are disseminated throughout the body. Immune defense mechanisms against HIV-1 include the innate immune system (dendritic cells, NK cells, macrophages, and cytokine network), the adaptive immune response (CD4+ and CD8+ T lymphocytes and B lymphocytes), and the intrinsic immune system (APOBEC3G, TRIM5α, tetherin, and SAMHD1). The most important role in evading the immune system is played by the accessory HIV-1 protein Nef. One of its most important roles is to downregulate MHC-I molecules so that they are degraded. This prevents lysis of infected cells by cytolytic T cells (CTLs). Nef also promotes activation of transcription factors and thus viral replication. Other immune defence mechanisms mediated by HIV-1 include mutations and/or masking of epitopes, latency, reverse transcriptase errors, and others. Due to the increasing adaptation of HIV-1, it is necessary to develop the most effective drug or vaccine to stop the spread of the virus or improve the quality of life of those infected. |
