it belongs to the Lentivirus genus of the retrovirus family, it infects CD4+ positive cells such as T-lymphocytes and macrophages , HIV-1 and HIV-2 are two distinct types of HIV

the first human retrovirus discovered was HTVL-1, Luc Montagnier and Francoise Barre-sinoussi were awarded the nobel prize for discovering HIV , the virus was initially named Lymphadenopathy-associated virus (LAV) and Human T-cell lymphotropiv Virus type lll (HTVL-III), HIV was identified in blood samples from the 1970s in the USA

international travel, blood transfusions using contaminated factors VIII, intravenous drug use, zoonotic transmission from infected chimpanzees

HIV is mainly transmitted through contact with blood or mucous membranes, sexual transmission of HIV has an estimated probability of 1 per 1000 contacts , the presence of other STDs can increase the risk of HIV transmission, intravenous drug use is an increasing cause of HIV transmission, particularly in eastern europe and asia

HIV-1 originated from chimpanzees infected with SIVcpz, HIV-2 is closely related to simultaneous Immunodeficiency Virus (SIVsm) from sooty mangabey monkeys , HIV-1 Group M is the most widespread and accounts for 98% of global infections , the first confirmed HIV-positive human sample dates back to 1959 in the democratic republic of congo

the number of new HIV infections has fallen from 3.3million in 1995 to 1.3 million in 2023, in 2023, approximately 30.7million people worldwide were accessing antiretroviral therapy , the UNAIDS 2016-2021 strategy aimed for 90% of people living with HIV to know their status, the global goal is to end the AIDS epidemic by 2030

rapid HIV tests detect antibodies to HIV, not the virus itself , HIV rapid tests can be used outside diagnostic laboratories , rapid HIV tests provide results in approximately 20 minutes, rapid HIV tests have an accuracy close to 99%

the total number of people living with HIV infection is greater than 30 million, the epidemic peaked in the late 1990s

HIV was first transmitted to humans in Cameroon, SIVcpz was the progenitor of HIV, SIVgor gave rise to HIV group N

HIV-2 does not contain the vpu gene, Tat and Rev are translated from singly spliced mRNAs, production of full length transcripts requires Tat

enhancement of virus infectivity, targets APOBEC3G for degradation , incorporation into the virus particle

CD4 positive T-cells, dendritic cells , glial cells

AIDS dementia complex, toxoplasma infection , syphilis

the protein is involved in nucleotide metabolism, it is a target for the Vpx protein , it is associated with an autoimmune disease

it is unregulated by interferon treatment , it is counteracted by SIVcpz Nef, it can be ubiquintinylated

reverse transcriptase inhibitors have two distinct modes of action, salvage therapy involved an intergrase inhibitor

maturation, capsid uncoating , membrane fusion , nuclear import

gp120 binds to the CD4 receptors on host cells, initiating the infection process, reverse transcriptase is responsible for converting the viral RNA into DNA, p7 is a nucleocapsid protein that protects the RNA genome , intergrase intergrates the viral DNA into the host cells genome

HIV is transmitted through macrophages in the urogenital and mucosa, where CCR5 , the virus is transmitted through mucosal membranes, where CCR5 is prevalent , NSI (non-syncytium inducing) viruses replicated in primary T-cells and macrophages , R5 viruses are selected during parental transmission (eg. bloodborne)

gp120 binds to CD4 receptors and initiates the infection process, gp41 faciliates fusion between the viral envelope and the host cell membrane , protease cleaves the long viral polyproteins into functional proteins during maturation , p17 provides structural support between the capsid and the envelope

the viral ssRNA is reverse transcribed into dSRNA by reverse transcriptase, HIV intergrates its DNA into the host cells genome to form a provirus, assembly and budding of HIV occur at the plasma membrane and through multivescular bodies

the half-life of infected CD4 cells is less than two days , viral replication in vitro is only detectable in activated T-cells , the immune system loses its ability to respond due to lymph node destruction

dendritic cells (DCs) play a key role in transmitting the virus to T-cells through the formation of a biological synapse, monocytes are primary target cells of HIV and present viral antigens to CD4 T-cells, HIV leads to loss of CD4 cell function even before CD4 depletion occurs

nucleoside analogue reverse transcriptase inhibitors (NRTIs), non-nucleotide reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs)

AZT (azidothymidine), dideoxycytidine

it consists of two molecules, P66 and P51, P66 is responsible for replicating the viral genome into double stranded DNA , P51 replicates in reverse transcriptase but does not replicate the viral genome

they prevent the mutation of the HIV virus particle , they cleave large polyproteins into functional proteins

fusion, reverse transcriptase, intergrase, maturation

nature of protective immunity (humours vs cellular), HIV genetic variability, especially in the env gene, ethical issues surrounding human clinical cells

maraviroc, T-20 (enfuvirtide, lenacapavir

maturation occurs after the virus is released from the host cell, protease inhibitors prevent the cleavage of polyproteins into functional proteins , HIV maturation involved the condensation of the viral core, maturation makes the virus infectious and ready to spread to other cells

hepatitis A and E viruses are non-enveloped , hepatitis B virus can lead to chronic infection and liver cancer

HCV is an enveloped virus, HCV infection often leads to chronic liver disease, the UK NHS aims to eliminate HCV by 2030

parenteral transmission is the most common route of HCV infection, HCV is efficiently transmitted through blood transfusion has been eliminated since 1992 due to screening, intravenous drug use is a major risk factor for HCV transmission

the HCV genome encodes a single poly protein , HCV belongs to the flavivirdae family

HCV genotype 1 is most common worldwide , egypt has an unusually high prevalence of HCV due to a past schistosomiasis treatment campaign , WHO aims to reduce HCV deaths to 140,000 by 2030

HCV infection can be confirmed using qRT-PCR, the HCV genotype can be determined through sequencing

the liver is one of the largest organs of the body, hepatocytes make up about 60% of the livers mass , bike production is one of the key functions of the liver

reuse of glass syringes during schistosomiasis treatment, use of poorly sterilised infection equipment , the use of antimony pottasium tartrate for schistosomiasis treatment

HCV was identified in 1970s as “non-A, non-B hepatitis”, HCV was successfully cloned and sequenced in 1991, chloroform was used in experiments to confirm HCV as an enveloped virus

direct-acting antivirals are effective in treating HCV , the UK has a screening program to identify HCV-positive individuals , WHO aims to increase the HCV cure rate to 90% by 2030

pHCV is a cDNA copy of the HCV genome , intrahepatic infection of HCV RNA into chimpanzees results in increasing viral titres, the polyprotein ORF contains structure and non-structural proteins

it lacks the structural proteins of HCV, it contains the neomycin phosphtransferase, NS3-NS5B are essential for RNA replication , mutations in NS5B can lead to loss of replication

NS3 has helicase and protease activity, the replication complex form cytoplasmic, membrane-bound compartments, NS4B is responsible for inducing membrane rearrangements known as the “membranous web”, NS5A plays a key role in viral RNA replication and interacts with host cell factors

the core protein bind girls RNA and is associated with lipid droplets , E1 and E2 are envelope glycoproteins responsible for receptor binding , p7 functions as an ion channel in the viral life cycle , NS2 has a role in virus assembly and release

NS3 contains a protease that cleaves non-structural proteins , NS3 required NS4A as a cofactor , NS5B catalysed the synthesis of both negative and positive RNA strands , both NS3 and NS5B are common targets are antivirals

HCV enters cells through receptor-mediated endocytosis, HCV replicated games place in membrane-bound cytoplasmic compartments , viral particles are transported in vesicles before release , lipoproteins are involved in the packaging of HCV particles

HCV particles are associated with lipoproteins in serum, LDL-R, SRB1 and tight junction proteins are involved in viral entry , claudia and CD81 are essential for HCV infection

direct-acting antivirals (DAAs) target NS3, NS5A and NS5B , NS5A inhibitors target viral replication and assembly , the JFH-1 strain was the first to complete the full HCV lifecycle in vitro , subgenomic replicons allow study of viral genome replication but not particle assembly

HCV infection can persist asa chronic infection in approximately 85% of cases, patients with chronic HCV infection may have normal levels of aminotransferase, chronic HCV infection is a major risk factors for hepatocellular carcinoma

jaundice , hepatic fibrosis , portal hypertension, hepatocellular carcinoma

fibrosis is caused by the deposition of extracellular matrix molecules such as collagen , hepatic stellate cells play a key role in fibrosis , cirrhosis is an advanced stage of fibrosis that can lead to liver failure

HCV blocks the insulin receptor signaling pathway , HCV promotes the production of cytokines like IL-18, insulin resistance caused by HCV contributed to accelerated fibrosis

HCV increases lipogenesis, HCV blocks fatty acid oxidation , HCV leads to steatosis , lipid accumulation in hepatocytes is genotype-specific

chronic inflammation and oxidative stress contribute to HCC development , cirrhosis is a major risk factor for HCC , HCV proteins such as NS5A and NS5B are implicated in HCC development , HCV-induced epigenetic modifications can predispose to HCC

binding to host receptors, entry via receptor-mediated endocytosis, translation and polyprotein processing , virus budding into intracellular vesicles

retroviruses have a single-stranded positive-sense RNA genome, reverse transcriptase converts viral RNA into double-stranded DNA , integration of viral DNA into the host genome is a key step in the retroviral cycle

encodes reverse transcriptase, which converts RNA to DNA, encodes integrate, which inserts viral DNA into the host genome, encodes protease, which cleaves viral polyproteins

long terminal repeats (LTRs) that regulate transcription, A primer binding site (PBS) for reverse transcriptase initiation , a polypurinentract (PPT) that serves as a primer for second-strand DNA synthesis

reverse transcription of the viral RNA genome into DNA , integration of proviral DNA into the host genome , viral RNA replication in the nucleus without DNA intermediate , assembly and release of new visions from the host cell membrane

tat, which enhances viral transcription, nef, which modulates immune invasion, vpu, which promotes viral release

the nucleocapsid surrounds and protects the viral RNA genome , the viral envelope is derived from the host cell membrane , the env gene encodes glycoproteins that mediate host cell entry

vision assembly at the host cell membrane , budding and acquisition of an envelope from the host , maturation involving cleavage of viral polyproteins by protease

the first effective HCV treatment was interferon monotherapy in 1990, combination therapy with peginterferon and ribavirin improved treatment effectiveness compared to interferon alone

interferon-a activates antiviral responses by inducing interferon-stimulated genes , ribavirin is a guanosine analogue incorporated into viral RNA, leading to mutations , the treatment includes both subcutaneous injections and oral administration

high relapse rates after treatment , severe side effects such as anaemia and reduced neutrophil levels , high cost of treatment

DAAs directly target viral proteins involved in HCV replication , combination DAA therapies are preferred to reduce resistance development , DAAs can target viral proteases, polymerases and other non-structural proteins

using DAAs in combination therapy to target multiple viral proteins , avoiding cross-resistance by selecting drugs from different classes , using highly potent DAAs that maintain effectiveness despite resistance mutations

NS5A inhibitors are highly potent, with very low effectiveness levels , first generation NS5A inhibitors has a low barrier to resistance , second generation NS5A inhibitors have improved resistance profiles and effectiveness