HIV virology and pathogenetic mechanisms of infection: a brief overview

Studies on HIV virology and pathogenesis address the complex mechanisms that result in the HIV infection of the cell and destruction of the immune system. These studies are focused on both the structure and the replication characteristics of HIV and on the interaction of the virus with the host. Continuous updating of knowledge on structure, variability and replication of HIV, as well as the characteristics of the host immune response, are essential to refine virological and immunological mechanisms associated with the viral infection and allow us to identify key molecules in the virus life cycle that can be important for the design of new diagnostic assays and specific antiviral drugs and vaccines. In this article we review the characteristics of molecular structure, replication and pathogenesis of HIV, with a particular focus on those aspects that are important for the design of diagnostic assays

The epidemic of HIV infection and AIDS, promotion of testing, and innovative strategies

In Europe, the incidence of new diagnoses of HIV infection in 2008 was 86.7 cases per one million population, and most cases were attributable to sexual transmission. In Italy, in 2007, the incidence was 60.0 cases per one million population (in the areas in which surveillance exists), and 73.7% of the cases were attributable to sexual transmission. At present, there are an estimated 170 000-180 000 persons living with HIV/AIDS in Italy, some of whom are unaware of being infected. Based on available epidemiological data and taking into consideration the level of risk of exposure to HIV, we describe several proposals for promoting access to HIV testing in diverse population groups and contexts, including some innovative approaches. The promotion of HIV testing is fundamental for public health and human rights and must be associated with treatment, care and prevention activities, which must be guaranteed for the entire population

Building collaborative networks for HIV/AIDS vaccine development: the AVIP experience

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Performance of V3-based HIV-1 sero subtyping in HIV endemic areas

HIV-1 serosubtyping based on reactivity to peptides from the V3 region of gp120 is a low-cost and easy to perform procedure often used in geographical areas with high prevalence and incidence of HIV infection. We evaluated the performance of V3-based serotyping on 148 sera from 118 HIV-1-infected individuals living in Uganda, with estimated dates of seroconversion. Of the 148 tested samples, 68 (46.0%) specifically reacted with only one of the V3 peptides included in the test (SP), 64 (43.2%) did not react with any peptide (NR) and 16 (10.8%) reacted with two or more peptides (CR). According to the estimated seroconversion date, the large majority of samples collected early after infection belonged to the NR group. These samples had also a low Avidity Index. In contrast, samples collected later after infection belonged mainly to CR and SP groups and had also a higher avidity index. These results indicate that the performance of V3-based assays depends on maturation of HIV-specific immune response and can be significantly lowered when these tests are carried out on specimens collected from recently infected individuals

Candidate HIV-1 Tat vaccine development: From basic science to clinical trials

No abstract available

Molecular characterization of HIV-1 subtype C gp-120 regions potentially involved in virus adaptive mechanisms

The role of variable regions of HIV-1 gp120 in immune escape of HIV has been investigated. However, there is scant information on how conserved gp120 regions contribute to virus escaping. Here we have studied how molecular sequence characteristics of conserved C3, C4 and V3 regions of clade C HIV-1 gp120 that are involved in HIV entry and are target of the immune response, are modulated during the disease course. We found an increase of "shifting" putative N-glycosylation sites (PNGSs) in the α2 helix (in C3) and in C4 and an increase of sites under positive selection pressure in the α2 helix during the chronic stage of disease. These sites are close to CD4 and to co-receptor binding sites. We also found a negative correlation between electric charges of C3 and V4 during the late stage of disease counteracted by a positive correlation of electric charges of α2 helix and V5 during the same stage. These data allow us to hypothesize possible mechanisms of virus escape involving constant and variable regions of gp120. In particular, new mutations, including new PNGSs occurring near the CD4 and CCR5 binding sites could potentially affect receptor binding affinity and shield the virus from the immune response. © 2014 Cenci et al

Kaposi's sarcoma‐associated herpesvirus serology in Europe and Uuganda: Multicentre study with multiple and novel assays

AbstractA multicentre study was undertaken to define novel assays with increased inter‐assay concordance, sensitivity, specificity and predictive value for serological diagnosis of human herpesvirus type 8 (HHV‐8) infection. A total of 562 sera from European and Ugandan human immunodeficiency virus (HIV)‐infected or uninfected individuals with or without Kaposi's sarcoma (KS) and blood donors were examined under code by 18 different assays in seven European laboratories. Sera from KS patients and all non‐KS sera found positive by at least 70%, 80%, or 90% of the assays were considered "true positive." The validity of the assays was then evaluated by univariate logistic regression analysis. Two immunofluorescence assays (IFA) for detection of antibodies against HHV‐8 lytic (Rlyt) or latent (LLANA) antigens and two enzyme‐linked‐immunosorbent assays (ELISA) (M2, EK8.1) for detection of antibodies against HHV‐8 structural proteins were found to be highly concordant, specific, and sensitive, with odds ratios that indicated a high predictive value. When used together, the two IFA (Rlyt‐LLANA) showed the best combination of sensitivity (89.1%) and specificity (94.9%). The performance of these assays indicate that they may be used for the clinical management of individuals at risk of developing HHV‐8 associated tumours such as allograft recipients. J. Med. Virol. 65:123–132, 2001. © 2001 Wiley‐Liss, Inc

Original Article

The pancreas taken from the frog (Rana nigromaculata) was fixed in 1% OsO_4 and sliced into ultrathin sections for electron microscopic studies. The following observations were made: 1. A great \u27number of minute granules found in the cytoplasm of a pancreatic cell were called the microsomes, which were divided into two types, the C-microsome and S-microsome. 2. Electron microsopic studies of the ergastoplasm showed that it is composed of the microsome granules and A-substance. The microsomes were seen embedded in the A-substance which was either filamentous or membranous. The membranous structure, which was called the Am-membrane, was seen to form a sac, with a cavity of varying sizes, or to form a lamella. 3. The Am-membrane has close similarity to α-cytomembrane of Sjostrand, except that the latter is rough-surfaced. It was deduced that the Am-membrane, which is smooth-surfaced, might turn into the rough-surfaced α-cytomembrane. 4. There was the Golgi apparatus in the supranuclear region of a pancreatic cell. It consisted of the Golgi membrane, Golgi vacuole and. Golgi vesicle. 5. The mitochondria of a pancreatic cell appeared like long filaments, and some of them were seen to ramify. 6. The membrane of mitochondria, i. e. the limiting membrane, consisted of the Ammembrane. The mitochondria contained a lot of A-substances, as well as the C-microsomes and S-microsomes. When the mitochondria came into being, there appeared inside them chains of granules, which appeared like strips of beads, as the outgrowths of the A-substance and the microsome granules attached to the Am-membrane. They are the so-called cristae mitochondriales. 7. The secretory granules originate in the microsomes. They came into being when the microsomes gradually thickened and grew in size as various substances became adhered to them. Some of the secretory granules were covered with a membrane and appeared like what they have called the intracisternal granule of Palade.It seemed that this was a phenomenon attendant upon the dissolution and liqutefaction of the secretory granule. 8. Comparative studies were made of the ergastoplasm of the pancreatic cells from the frogs in hibernation, the frogs artificially hungered, the frogs which were given food after a certain period of fasting, the frogs to which pilocarpine was given subcutaneously, and the very young, immature frogs. The studies revealed that the ergastoplasm of the pancreatic cells greatly varied in form with the difference in nutritive condition and with different developmental stages of the cell. The change in form and structure occured as a result of transformation of the microsomes and A-substance. The ergastoplasm, even after it has come into being, might easily be inactivated if nutrition is defective. The ergastoplasm is concerned in the secretory mechanism, which is different from the secretory phenomenon of the secretory granules. It would seem that structurally the mitochondria have no direct relation to this mechanism

Suggested strategies for the laboratory diagnosis of HIV infection in Italy

HIV/AIDS surveillance data indicate that, in 2008, approximately one-fourth of all HIV infections in adults remain undiagnosed in Italy and that close to 60% of Aids diagnosed individuals discovered their seropositivity at the diagnosis of AIDS. Late diagnosis of HIV infection is associated with increased mortality and morbidity and increased cost to healthcare services. From a public health perspective, knowledge of HIV status is associated with a reduction in risk behaviour. Thus, a routine screening for HIV infection is important for both a better prognostic outcome, and control of HIV spreading in the population. In Italy there are not shared guidelines for the laboratory diagnosis. In this paper, we suggest two algorithms that can be adopted for the diagnosis of HIV infection in individuals undergoing HIV testing